Podcasts about Acei

THE LANCET 2003;362:767-771Background: Angiotensin II which plays a role in ventricular remodeling and progression of heart failure can be produced by pathways independent of angiotensin convening enzyme. Preliminary studies showed that the combination of angiotensin II blockers with angiotensin-converting enzyme inhibitors (ACEi) improves hemodynamics and reduces ventricular remodeling.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added trial sough to assess if adding the angiotensin-receptor blocker (ARB), candesartan, to ACEi could improve outcomes in patients with systolic heart failure.Patients: Eligible patients had left ventricular ejection fraction of 40% or less within the previous 6 months, and NYHA class II, III or IV symptoms. Patients with NYHA class II symptoms had to have cardiac-related hospitalization within 6 months. Patients also had to have treatment with ACEi at a constant dose for at least 30 days.Exclusion criteria were not provided in the main manuscript.Baseline characteristics: Patients were recruited from 618 centers in 26 countries. The trial randomized 2,548 patients – 1,276 randomized to receive candesartan and 1,272 to receive placebo.The average age of patients was 64 years and 79% were men. The average left ventricular ejection fraction was 28%. Cardiomyopathy was ischemic in 62% of the patients. The NYHA class was II in 24% of the patients, III in 73% and IV in 3%.Approximately 48% had hypertension, 30% had diabetes, 56% had prior myocardial infarction, 9% had stroke, 27% had atrial fibrillation and 17% were current smokers.At the time of enrollment, 90% were taking a diuretic, 58% were taking digoxin, 55% were taking beta-blockers, 17% were taking spironolactone and all but two patients were taking ACEi.Procedures: The trial was double-blinded. Patients were assigned in a 1:1 ratio to receive candesartan starting at 4 or 8mg once daily or placebo. The treatment was doubled every two weeks to a target dose of 32mg once daily.After randomization, follow up occurred at 2, 4, and 6 weeks, 6 months and every 4 months thereafter.Endpoints: The primary outcome was a composite of cardiovascular death or heart failure hospitalizations. All deaths were classified as cardiovascular unless there was a clear non-cardiac cause.Analysis was performed based on the intention-to-treat principle. The estimated sample size to have 80% power at 5% alpha was 2,300 patients. The sample size calculation assumed 16% relative risk reduction in the primary outcome with candesartan assuming an 18% annual event rate in the placebo arm.Results: The median follow up time was 41 months. The mean candesartan daily dose was 24mg at 6 months.Candesartan reduced the primary endpoint of cardiovascular death or heart failure hospitalizations (37.9% vs 42.3%, adjusted HR: 0.85, 95% CI: 0.75 – 0.96; p= 0.01). Candesartan reduced the individual components of the primary outcome - (23.7% vs 27.3%; p= 0.021) for cardiovascular death and (24.2% vs 28.0%; p= 0.018) for heart failure hospitalizations. There was no significant reduction in all-cause death (29.5% with candesartan vs 32.4%; p= 0.105). The number of patients who had any hospitalization was similar in both groups (66.8% with candesartan vs 67.5%; p= 0.7), however, the total number of hospitalizations was lower with candesartan (2,462 vs 2,798; p= 0.023).Serum creatinine at least doubled in 7% of the patients in the candesartan group vs 6% in the placebo group. In the subset of patients taking spironolactone, serum creatinine at least double in 11% of the patients taking candesartan compared to 4% of the patients taking placebo.Hyperkalemia, defined as serum potassium of 6 mmol/L or higher, occurred in 3% of the patients in the candesartan group vs 1% in the placebo group. In the subset of patients taking spironolactone, hyperkalemia occurred in 4% of the patients taking candesartan compared to 1% of the patients taking placebo.There were two cases of angioedema in the candesartan group and three in the placebo group. All patients were taking an ACEi.There were no significant subgroup interactions, including in patients taking both beta-blockers and ACEi at baseline.Conclusion: In patients with systolic heart failure, adding candesartan to an ACEi reduced the primary composite outcome of cardiovascular death or heart failure hospitalizations with a number needed to treat of approximately of 23 patients over 41 months of follow up. The total number of all-cause hospitalizations was reduced by 336 with candesartan. All-cause death was not significantly reduced with candesartan.While the results of the trial appear impressive, the high number of adverse outcomes with candesartan in patients taking spironolactone is concerning. Spironolactone led to significant reduction in all-cause mortality in patients with systolic heart failure, as seen in the RALES trial, and should be prioritized over adding candesartan. Notably, fewer than 20% of patients in the trial were on spironolactone at baseline; if more had been, the incremental benefit of candesartan would likely have been reduced due to an increased risk of adverse effects from triple neurohormonal blockade (ACEi, ARBs, and mineralocorticoid receptor antagonists). Furthermore, spironolactone acts by blocking the aldosterone receptor, which is downstream in the renin–angiotensin–aldosterone system. Since candesartan blocks angiotensin II upstream in the same pathway, simultaneous inhibition at multiple points may lead to diminishing benefit.Finally, the differences observed in the subgroup of patients on beta-blockers between this trial and Val-HeFT remain unclear and may simply reflect the play of chance. As we previously discussed, patients receiving both an ACEi and beta-blockers had worse outcomes with valsartan in the Val-HeFT trial.Cardiology Trial's Substack is a reader-supported publication. 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N Engl J Med 2001;345:1667-1675Background: Angiotensin II is a peptide hormone that is part of the renin–angiotensin–aldosterone system (RAAS). Angiotensin II is a potent vasoconstrictor and growth-stimulating hormone. Data suggested that it plays a role in ventricular remodeling and progression of heart failure. Although treatment with angiotensin-converting enzyme inhibitors (ACEi) reduce angiotensin II levels, physiologically active levels of angiotensin II may persist despite long-term therapy.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.The Valsartan Heart Failure Trial (Val-HeFT) sough to assess whether the angiotensin-receptor blocker valsartan, could reduce mortality and morbidity when added to optimal medical therapy in patients with systolic heart failure.Patients: Eligible patients had left ventricular ejection fraction less than 40% and left ventricular dilation, in addition to having clinical heart failure for at least 3 months with NYHA class II, III or IV symptoms. Patient also had to have been receiving a fixed-dose drug regimen for at least two weeks, that could include ACEi, diuretics, digoxin, and beta-blockers.There were many exclusion criteria. We mention some here: Postpartum cardiomyopathy, acute myocardial infarction within 3 months, coronary artery disease likely to require intervention, serum creatinine >2.5 mg/dL and life expectancy less than 5 years.Baseline characteristics: Patients were recruited from 302 centers in 16 countries. The trial randomized 5,010 patients – 2,511 randomized to receive valsartan and 2,499 to receive placebo.The average age of patients was 63 years and 80% were men. The average left ventricular ejection fraction was 27%. Cardiomyopathy was ischemic in 57% of the patients. The NYHA class was II in 62% of the patients, III in 36% of the patients and IV in 2%.Approximately 26% had diabetes and 12% had atrial fibrillation.At the time of enrollment, 86% were taking a diuretic, 67% were taking digoxin, 35% were taking beta-blockers, and 93% were taking ACEi.Procedures: The trial was double-blinded. The trial had an initial run-in period for 2 - 4 weeks where patients received placebo twice daily. This was performed to confirm patients' eligibility, clinical stability and compliance.Patients were assigned in a 1:1 ratio to receive valsartan or placebo. Randomization was stratified according to whether or not they were receiving a beta-blocker.Valsartan was started at a dose of 40 mg twice a day, and the dose was doubled every two weeks to the target dose of 160 mg twice a day. Placebo doses were adjusted in a similar way.Follow up occurred at 2, 4, and 6 months and every 3 months thereafter.Endpoints: The trial had two primary end points. The first was all-cause mortality. The second was the combined end point of mortality and morbidity, which was defined as cardiac arrest with resuscitation, hospitalization for heart failure, or administration of intravenous inotropic or vasodilator drugs for four hours or more without hospitalization.The estimated sample size was 5,000 patients. The sample size calculation assumed 20% relative risk reduction in mortality with valsartan assuming 906 patients would die during the trial. This sample size would provide the trial 90% power at 0.02 alpha. Alpha was 0.02 instead of the traditional 0.05 since the trial had two primary endpoints and to adjust for the interim analyses.Results: The target valsartan dose of 160 mg twice a day was achieved in 84% of the patients. The reduction in systolic blood pressure was greater with valsartan vs placebo – mean of 5.2 ± 15.8 mm with valsartan compared to 1.2 ± 14.8 mm Hg with placebo, at 4 months.All-cause mortality was not different between both groups (19.7% with valsartan vs 19.4% with placebo, RR: 1.02, 95% CI: 0.88 – 1.18; p= 0.80). The second co-primary endpoint was reduced with valsartan (28.8% vs 32.1%, RR: 0.87, 95% CI: 0.77 – 0.97; p= 0.009). This was driven by reduction in hospitalizations for heart failure (13.8% vs 18.2%). Cardiac arrest with resuscitation was 0.6% with valsartan and 1.0% with placebo. All-cause hospitalization was numerically lower with valsartan, however, this was not statistically significance (2,856 vs 3,106; p= 0.14). The mean change in ejection fraction was higher with valsartan (4.0% vs 3.2%; p= 0.001). More patients had improvement in NYHA classification with valsartan (23.1% vs 20.7%; p

N Engl J Med 2001;344:1651-1658Background: The MERIT-HF trial demonstrated the efficacy of the selective beta blocker metoprolol CR/XL for well selected patients with chronic systolic heart failure who were on optimal therapy with an ACEi and diuretic. The trial randomized nearly 4,000 patients and was stopped early due to the benefit of the drug on all-cause mortality but it also reduced major morbidity as indicated by significant reductions in hospitalization. It represented the first large scale trial to show a morbidity and mortality benefit for beta blockers in patients with chronic systolic heart failure. Prior to MERIT-HF, the nonselective beta blocker carvedilol reduced morbidity and mortality in a smaller trial of patients with chronic stable heart failure. Limitations of the trial included its size and the fact that it was not originally designed to test mortality. Furthermore, it was stopped early without clearly prespecified stopping rules and 8% of total patients selected for participation in the trial were excluded prior to randomization after a 2 week, open-label run-in phase with the study drug. During the run-in period, 24 patients (2%) experienced worsening heart failure or death and were excluded from participation in the trial - the difference in total deaths between groups was 9 when the trial was stopped. In our opinion, the results of this trial were far from definitive and there are theoretical reasons why selective and nonselective beta blockers could have different effects on cardiac outcomes.The primary difference between selective and nonselective beta blockers lies in their specificity of action; while both types block adrenaline from binding to beta receptors on nerves, selective beta blockers primarily affect those found in the heart whereas nonselective ones also impact those located in the lungs and blood vessels. In the lungs, adrenaline causes bronchodilation and in the blood vessels, vasoconstriction. Thus, nonselective beta blockers also reduce afterload, which can improve cardiac hemodynamics in the failing heart.The Carvedilol Prospective Randomized Cumulative Survival Study was a large-scale trial that sought to test the hypothesis that the nonselective beta blocker carvedilol reduces mortality in patients with chronic stable heart failure who are on optimal treatment.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients: Patients with “severe chronic heart failure” were recruited from 334 sites in 21 countries. Severe chronic heart failure was defined by the presence of dyspnea or fatigue at rest or on minimal exertion for at least 2 months and a LVEF of

Listen as Michael S. Blaiss, MD provides case-based perspectives on chronic cough recognition, burden, management, and pathophysiology and describes the evolving treatment landscape for refractory chronic cough.PresenterMichael S. Blaiss, MDClinical Professor of PediatricsDivision of Allergy-ImmunologyMedical College of Georgia at Augusta UniversityAugusta, GeorgiaLink to full program: https://bit.ly/4kweynG

Circulation 1999;100:2312-2318Background: The CONSENSUS and SOLVD trials established the effectiveness of angiotensin converting enzyme inhibitors (ACEi) in reducing mortality and morbidity in patients with systolic heart failure. Both trials used enalapril with a target dose of 20mg twice a day (max dose) in the CONSENSUS trial and 10mg twice a day (medium dose) in the SOLVD trials. In real-world settings, ACEi are sometimes prescribed at lower doses, likely reflecting concerns about adverse effects or patients' tolerance. It was unclear whether the benefit from low doses of ACEi is comparable to high doses.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.The Assessment of Treatment with Lisinopril and Survival (ATLAS) trial sought to assess the efficacy and safety of low vs high doses of ACE inhibition in patients with systolic heart failure.Patients: Eligible patients had left ventricular ejection fraction of 30% or less and had NYHA class II, III or IV despite treatment with diuretics for two or more months.Patients were excluded if they had any of the following: Acute coronary syndrome or revascularization procedure within 2 months, history of sustained or symptomatic ventricular tachycardia, known intolerance to ACEi, serum creatinine >2.5 mg/dL, or any noncardiac condition that could limit survival.Baseline characteristics: The trial randomized 3,164 patients – 1,596 randomized to the low-dose arm and 1,568 to the high dose arm.The average age of patients was 64 years and 80% were men. The average left ventricular ejection fraction was 23%. Cardiomyopathy was ischemic in 65% of the patients. The NYHA class was II in 16% of the patients, III in 77% and IV in 7%.Data on baseline comorbid conditions were not provided in the main manuscript.Procedures: The study was double blinded. At the beginning of the study, all patients received open-label lisinopril for four weeks to assess who is able to tolerate the drug. Patients who were able to tolerate lisinopril 12.5 mg to15 mg daily for two or more weeks were randomized in a 1:1 ratio to receive low-dose or high-dose ACEi. The target dose of lisinopril in the lose dose group was 2.5 to 5.0mg daily and was 32.5 to 35mg daily in the high dose group.All patients received open-label lisinopril 2.5 to 5mg daily. This dose was selected by the investigator. In addition, patients received up to three 10mg tablets of lisinopril or matching placebo.Endpoints: The primary endpoint was all-cause mortality. Secondary end points included cardiovascular mortality, all-cause hospitalization and cardiovascular hospitalizations.Analysis was performed based on the intention-to-treat principle. The estimated sample size was 3,000 patients. This sample size had 90% power at 5% alpha to detect 15% relative risk difference in the mortality between both treatment groups assuming 19% 1-year mortality in the high dose group.Results: Of the 3,793 patients who entered the initial open-label tolerability phase, 83.4% were randomized. A total of 176/3,793 (4.6%) were withdrawn for possible side effects. The median follow-up time was 46 months.Target doses were achieved in 92.7% of the patients in the low-dose group and 91.3% in the high-dose group. Study medication was discontinued by 30.6% of patients in the low-dose group and 27.2% in the high-dose group.All-cause mortality was not significantly different between both treatment groups (44.9% with low dose vs 42.5% with high dose, HR: 0.92, 95% CI: 0.82 – 1.03; p= 0.128). Cardiovascular mortality was numerically lower in the high dose group but this was not statistically significant (37.2% vs 40.2%, HR: 0.90, 95% CI: 0.81 – 1.01; p= 0.073). All-cause hospitalization was lower in the high dose group (3,819 hospitalizations vs 4,397; p= 0.021). Hospitalizations for cardiac causes and hospitalizations for heart failure were also lower in the high dose group (2,456 vs 2,923; p= 0.05) and (1,199 vs 1,576; p= 0.002), respectively.Patients in the high-dose group experienced more dizziness (19% vs 12%), more hypotension (11% vs 7%), more worsening renal function (10% vs 7%), and more hyperkalemia (6% vs 4%), but reported less cough (11% vs 13%) and had less hypokalemia (1% vs 3%).There were no significant subgroup interactions for the primary outcome.Conclusion: In patients with systolic heart failure, high dose ACE inhibition did not significantly reduce mortality compared to low-dose but it led to significantly less hospitalizations. In this trial of 3,164 patients and with a median follow up of 46 months, there were 578 less hospitalizations in the high dose group.Based on these results, we recommend up-titrating ACEi and use higher doses if tolerated. Although, side effects were more common in the high dose group, these can generally be managed with reducing the dose in the outpatient settings.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Lancet 1999;353:2001-07Background: Beta-blockers directly reduce cardiac contractility and myocardial oxygen demand. For decades, they were avoided in patients with acute and chronic heart failure over concerns they would facilitate decompensation of the condition. The therapeutic cornerstones of treatment, prior to the modern era of clinical trials, focused on managing symptoms and quality of life with diuretics and inotropic agents like digoxin; however, new paradigms were arising that focused on addressing neurohormonal mechanisms of chronic disease that were over-activated in the failing heart. The first major success came with inhibition of the renin angiotensin aldosterone system with angiotensin converting enzyme inhibitors whose effect on mortality for patients with mild and severe forms of chronic heart failure were demonstrated in the V-HEFT II, CONSENSUS, and SOLVD trials. Additional benefits were demonstrated with the mineralocorticoid receptor antagonist spironolactone in the RALES trial. These drug classes primarily work by reducing afterload and volume retention. Appreciating why they work for improving cardiac performance and managing symptoms in heart failure patients is straightforward when we consider the major factors that effect cardiac stroke volume - preload, afterload and contractility; however, it is also noteworthy the effects these agents have on sudden death. How beta-blockade benefits the failing heart is less obvious (outside prevention of sudden death). Mechanistic studies in patients with chronic heart failure have consistently shown that when beta blockers are used for more than 1 month, left ventricular function improves. Beta blocker therapy appears to restore the density of beta-adrenergic receptors after they have been downregulated by the chronic overactivity of the sympathetic nervous system. The first major placebo-controlled RCT to demonstrate a mortality benefit used the non-selective beta blocker carvedilol. The trial was small and not originally designed to test mortality and was stopped early without clearly predefined stopping rules. Furthermore, 8% of total patients selected for participation in the trial were excluded prior to randomization after a 2 week, open-label run-in phase with the study drug, which saw 2% of all patients experience worsening heart failure or death representing 24 patients (the difference in total deaths between groups was 9 when the trial was stopped). The Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) was the first large scale trial designed to test the hypothesis that beta-blockade with metoprolol controlled/extended release (CR/XL) added to optimum medical therapy reduces mortality in patients with chronic systolic heart failure.Patients: Patients were recruited from 313 sites in 13 European countries and the United States. Eligible patients were men and women between the age of 40 to 80 years with symptomatic heart failure (NYHA class II-IV) for >/= 3 months before randomization. They had to be on a diuretic and ACE inhibitor for at least 2 weeks. Other drugs, including digoxin, could also be used. Patients also had to have an EF of /=68 beats per minute.Patients were excluded if: they had an MI or unstable angina within 28 days; had an indication or contraindication for treatment with beta-blocker; beta blockade within 6 weeks; heart failure due to systemic disease (i.e., amyloidosis) or alcohol abuse; scheduled or performed cardiac transplant; an ICD; procedures such as CABG or PCI planned or performed in the past 4 months; 2nd or 3rd degree AV block unless a pacemaker was present; unstable or decompensated heart failure defined by pulmonary edema or hypoperfusion or supine systolic BP 25% deviation of the number of observed versus expected consumed placebo tablets during the run-in period.Baseline characteristics: The mean age of patients was 64 years and approximately 78% were male. Slightly more than 30% of patients were above the age of 70. The average EF was 28%. The average SBP was 130 mmHg and heart rate was 82 bpm. Most patients had mild to moderate heart failure, with 41% in NYHA Class II, 56% in Class III, and only 3% in Class IV. Ischemic cardiomyopathy accounted for 65% of cases and nonischemic causes accounted for 35%. Most patients were on an ACE inhibitor or ARB (95%) and diuretic (90%). Digoxin was used in 63%. Trial procedures: Prior to randomization, the study was preceded by a single-blind, 2-week placebo run-in period. Patients meeting eligibility were then randomized to placebo or metoprolol CR/XL. The starting dose of placebo or metoprolol CR/XL was 12.5 mg daily for patients in NYHA class III or IV and 25 mg daily for patients in NYHA class II. The dose was doubled every 2 weeks until the target dose of 200 mg daily was reached. Patients were followed every 3 months.Endpoints: The primary outcome was all-cause mortality. It was estimated that 3,200 patients would need to be followed for 2.4 years to detect a 30% relative reduction in mortality based on annual mortality rate of 9.4% in the placebo group. This would achieve at least 80% power with a 2-sided alpha of 0.04. Patients were recruited faster then planned and so the final sample size of 3,991 patients increased the power of the study.The study was monitored by an independent safety committee and predefined stopping rules for efficacy were based on all-cause mortality, done when 25%, 50%, and 75% of expected deaths had occurred. Results: The trial was stopped early after the 2nd preplanned interim analysis when 50% of expected deaths had occurred. The mean duration of follow-up at the time of stopping was 1 year. The mean daily dose of metoprolol CR/XL was 159 mg once daily, with 87% receiving 100 mg or more and 64% receiving the target dose of 200 mg daily. In the placebo group, the corresponding values were 179 mg daily, 91% and 82%. The study drug was discontinued permanently in 14% of patients in the metoprolol group and 15% in the placebo group. Six months after randomization, heart rate decreased by 14 bpm in the metoprolol group compared to only 3 bpm in the placebo group. Systolic blood pressure decreased less in the metoprolol group (-2.1 vs 3.5 mmHg).Compared to placebo, metoprolol significantly reduced all-cause mortality (7.3% vs 10.8%; RR 0.66; 95% CI 0.53—0.81). Cardiovascular mortality accounted for 91% of all deaths; with sudden death accounting for 58% and death from worsening heart failure accounting for 24% of all deaths. All 3 of these causes of death were significantly reduced by metoprolol. The relative and absolute effects on death were greatest for patients with NYHA class III heart failure.Conclusions: In this trial of stable patients with mild to moderate chronic systolic heart failure, who were optimized on an ACEi or ARB and diuretic, metoprolol CR/XL significantly reduced all-cause mortality. Approximately 30 patients would need to be treated with metoprolol compared to placebo for 1 year to prevent 1 death. This trial represents a significant win for beta blockade in patients with chronic systolic heart failure. While the NNT in this trial is slightly higher than in SOLVD, it is important to appreciate that follow-up time in SOLVD was more than 3x longer. Limitations to external validity in this trial include the run-in period and stringent inclusion and exclusion criteria. Our enthusiasm is also tempered by early stopping, which has been found to be associated with false positive or exaggerated results but this concern is mitigated to some extent in this trial because the rules for early stopping were clearly defined in the protocol.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

N Engl J Med 1999;341:709-717Background: The renin–angiotensin–aldosterone system (RAAS) is activated in patients with systolic heart failure. While this activation initially helps increase blood volume and maintains blood pressure, chronic activation promotes cardiac fibrosis and remodeling. In patients with systolic heart failure, inhibition of the RAAS with angiotensin-converting enzyme inhibitors (ACEi) significantly reduced mortality and morbidity, as seen in the CONSENSUS and SOLVD trials.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Preliminary data suggested that adding the aldosterone-receptor blocker spironolactone to ACEi, reduced the levels of atrial natriuretic peptide and did not lead to serious hyperkalemia.The Randomized Aldactone Evaluation Study (RALES) sought to test the hypothesis that spironolactone would significantly reduce the risk of all-cause death in patients with severe systolic heart failure.Patients: Eligible patients had left ventricular ejection fraction of 35% or less, had NYHA class IV heart failure within the 6 months before enrollment and NYHA class III or IV at the time of enrollment, and were treated with ACEi (if tolerated) and a loop diuretic.Patients were excluded if they had primary operable valvular disease (other than mitral or tricuspid regurgitation), congenital heart disease, unstable angina, primary liver failure, active cancer or any life-threatening condition, other than heart failure, prior heart transplant or awaiting heart transplant, serum creatinine >2.5 mg/dL, or serum potassium > 5.0 mmol/L.Baseline characteristics: Patients were recruited from 195 centers in 15 countries. The trial randomized 1,663 patients – 822 randomized to receive spironolactone and 841 to receive placebo.The average age of patients was 65 years and 73% were men. The average left ventricular ejection fraction was 25%. Cardiomyopathy was ischemic in 55% of the patients and non-ischemic in the rest. The NYHA class was III in 71% of the patients and IV in 29%.Data on baseline comorbid conditions were not provided.At the time of enrollment, 100% were taking loop diuretics, 94% were taking ACEi, 73% were taking digitalis, and 10% were taking beta-blockers. The mean daily dose of ACEi were as following: 63mg for captopril, 15mg for enalapril, and 14mg for lisinopril.Note: Max daily dose is 450mg for captopril, 40mg for enalapril, and 40mg for lisinopril.Procedures: The trial was double-blinded. Patients were assigned in a 1:1 ratio to receive spironolactone 25mg PO daily or placebo.The dose could be increased to 50mg daily after 8 weeks of treatment, If the patient had worsening heart failure and had no evidence of hyperkalemia. In the event of hyperkalemia, the dose could be lowered to 25 mg every other day. Laboratory testing including potassium were performed every 4 weeks for the first 12 weeks, then every 3 months for up to 1 year and every 6 months thereafter until the end of the study.Endpoints: The primary outcome was all-cause death. Secondary end points included death from cardiac causes, hospitalization for cardiac causes and change in the NYHA class.Analysis was performed based on the intention-to-treat principle. The planned sample size was not mentioned in the methods. However, the results mention that recruitment was complete. The sample size calculation assumed 38% mortality rate in the placebo group and that spironolactone would reduce mortality by 17% (relative risk reduction). The power of the study was set at 90% with a two-sided alpha of 5%.Results: Recruitment was complete in Dec, 1996 with follow up planned through Dec, 1999. However, the study was stopped early on Aug, 1998 after interim analysis showed significant reduction in mortality with spironolactone. The mean follow up time was 24 months. After 24 months of follow up, the mean daily dose of spironolactone was 26 mg.Spironolactone reduced all-cause death (35% vs 46%, RR: 0.70, 95% CI: 0.60 - 0.82; p< 0.001). Death from cardiac causes was also reduced with spironolactone (27% vs 37%, RR: 0.69, 95% CI: 0.58 - 0.82; p

Podcast summary of articles from the March 2025 edition of the Journal of Emergency Medicine from the American Academy of Emergency Medicine.  Topics include pediatric airways, IV contrast induced nephropathy, toxic mushrooms, TXA for ACEI angioedema, bias in patient surveys, and hyperbaric oxygen therapy.  Guest speaker is Dr. Matthew Carvey.

N Engl J Med 1991;325:293-302N Engl J Med 1992;327:685-691Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Background: Systolic heart failure affects millions worldwide and is associated with high mortality and morbidity. If left untreated, the one-year mortality ranges from 15-50%, depending on the severity of the disease.The CONSENSUS trial found mortality benefit with the use of the angiotensin converting enzyme inhibitor (ACEi) enalapril in patients with New York Heart Association (NYHA) class IV heart failure. Data on less severe heart failure were lacking.The Studies of Left Ventricular Dysfunction (SOLVD) sought to assess whether an ACEi, enalapril, would reduce mortality in patients with low left ventricular ejection fractions defined as 35% of less.Patients: Eligible patients had left ventricular ejection fraction of 35% or less. The ejection fraction was measured using radionuclide techniques in 68% of the patients, contrast angiography in 11%, and two-dimensional echocardiography in 21%.Patients were excluded if they were over 80 years of age, or if they had significant valvular disease requiring surgery, unstable angina pectoris, angina requiring revascularization procedures, myocardial infarction during the previous month, severe pulmonary disease, serum creatinine >2 mg/ dl, or any other disease that might significantly impact survival.At the end of the run-in period for placebo, patients who had overt congestive heart failure were enrolled in the Treatment trial, and patients who were not having overt congestive heart failure were enrolled in the Prevention trial.Baseline characteristics: Patients were recruited from 83 hospitals linked to 23 centers in the United States, Canada, and Belgium.The Treatment trial randomized 2,569 patients – 1,285 patients randomized to receive enalapril and 1,284 randomized to receive placebo. The average age of patients was 61 years and 80% were men. The average left ventricular ejection fraction was 25%. Approximately 42% had hypertension, 26% had diabetes, 71% had ischemic heart disease and 22% were current smokers. The NYHA class was I in 11% of the patients, II in 57% of the patients, III in 30% and IV 2%. At the time of enrollment, 8% were taking beta-blockers, 67% were taking digitalis, 85% were taking diuretics, 9% were taking potassium-sparing diuretics and 51% were taking vasodilators (other than ACEi).The Prevention trial randomized 4,228 patients – 2,111 patients randomized to receive enalapril and 2,117 randomized to receive placebo. The average age of patients was 59 years and 89% were men. The average left ventricular ejection fraction was 28%. Approximately 37% had hypertension, 15% had diabetes, 83% had ischemic heart disease and 23% were current smokers. The NYHA class was I in 67% of the patients and II in 33%. At the time of enrollment, 24% were taking beta-blockers, 12% were taking digitalis, 17% were taking diuretics, 4% were taking potassium-sparing diuretics and 46% were taking vasodilators (other than ACEi).Procedures: A total of 7,402 patients were deemed eligible across both the Treatment and Prevention trials.Eligible patients for either trial entered a run-in and stabilization phase. Patients were given enalapril 2.5 mg twice daily in a single-blind fashion for 2 - 7 days to identify patients who could not tolerate even a small dose of the drug or those who were unable to comply with the regimen. A total of 310/7402 patients (4.2%) were excluded from the study during this phase. Following the active dosing phase, patients were placed on a regimen of matching placebo in a single-blind manner for 14 - 17 days. This allowed identification of individuals whose clinical condition deteriorated after drug withdrawal or who demonstrated poor compliance. During this phase, 295/ 7,092 patients (4.2%) were excluded from the study.At the end of the run-in period for placebo, patients who had overt congestive heart failure were enrolled in the Treatment trial, and patients who were not having overt congestive heart failure were enrolled in the Prevention trial.After that patients were randomized in a 1:1 ratio to receive enalapril or placebo.Treatment with enalapril or placebo was initiated at 2.5 mg or 5 mg twice daily, based on the patient's clinical status and physician judgment. The dose was titrated up to 10 mg twice daily if tolerated without symptomatic hypotension or worsening renal function. After randomization, follow-up visits occurred at two weeks, six weeks, four months, and every four months thereafter until study completion.Endpoints: The primary outcome for both trials was all-cause mortality. Heart failure hospitalization was assessed as a secondary outcome.The estimated sample size was 2,500 patients for the treatment trial and 4,600 for the prevention trial. These sample sizes would provide 90% power at 5% two-sided alpha to detect 25% relative risk reduction in mortality, with the use of enalapril. The estimated 3-year mortality in the control group was 32% in the Treatment trial and 17% in the Prevention trial.Authors reported risk reduction which was calculate as (1 – relative risk)*100.Results: A total of 39,924 patients with a left ventricular ejection fraction of 35% or less were identified. Of these, 6.4% were enrolled in the Treatment trial and 7.4% in the Prevention trial. Among the excluded patients, the main reasons were prior use of an ACEi (28%), cardiovascular problems (12%), contraindications to using ACEi (11%), lack of patient consent (11%), administrative reasons (21%), cancer or other life-threatening illnesses (12%), and other miscellaneous reasons (5%).The average follow up time was 41.4 months in the Treatment trial and 37.4 months in the Prevention trial.In the Treatment trial, enalapril reduced all-cause mortality (35.2% vs 39.7%, risk reduction: 16%, 95% CI: 5% – 26%; p< 0.0036). The majority of deaths (89%) were cardiovascular and the majority of these (79%) were heart failure or arrhythmia related. Enalapril also reduced all-cause hospitalization (69.5% vs 74.0%; p= 0.006). The total number of hospitalizations for heart failure was also reduced with enalapril – 683 vs 971. Subgroup analysis showed a numerical increase in death, with enalapril, in patients with an ejection fraction of 30-35% - this was not statistically significant.In the Prevention trial, enalapril did not have a significant effect on mortality (14.8% with enalapril vs 15.8% with placebo, risk reduction: 8%, 95% CI: -8% – 21%; p= 0.30). Enalapril significantly reduced the development of heart failure (20.7% vs 30.2%; p< 0.001). Total number of hospitalizations for heart failure was also significantly reduced with enalapril – 306 vs 454. The reduction in the development of heart failure was seen across all ejection fractions below 35%, although the benefit was larger with lower ejection fractions.In both trials, the benefit of enalapril was seen early after treatment initiation.Conclusion: In patients with left ventricular ejection fraction of 35% or less and overt congestive heart failure, enalapril reduced all-cause mortality with a number needed to treat of approximately 22 patients. In patients with a left ventricular ejection fraction of 35% or less and without overt congestive heart failure, enalapril had no significant effect on mortality but it reduced the development of heart failure with an number needed to treat of approximately 11 patients.The SOLVD trials provide strong evidence supporting the use of ACEi in patients with systolic heart failure. The role of ACEi in systolic heart failure has been examined across diverse patient groups, and the totality of evidence consistently supports their use. However, when examining the SOLVD trials in isolation, it is important to recognize the selective nature of enrollment, which limits the trials' external validity. Additionally, the use of a run-in period introduces bias in favor of enalapril, although this concern is less significant when the primary outcome is all-cause mortality.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

In this podcast recorded in early March, David Phizackerley (DTB Editor-in-Chief) and James Cave (DTB Editor-in-Chief Emeritus) provide an overview of the April 2025 issue of DTB. The editorial discusses concerns over the use of feminist empowerment messages to sell tests and treatments. A DTB Select item summarises the results of an observational study that assessed the association between initiation of a triptan and the risk of myocardial infarction or stroke. The main article provides an overview of initiating angiotensin-converting enzyme inhibitors or angiotensin-II receptor antagonists in adults with CKD, highlighting current guideline recommendations and providing a practical approach to dealing with the challenges associated with their use.   Links Health Innovation Network: https://thehealthinnovationnetwork.co.uk/news/launch-of-new-game-changing-guide-to-tackle-overprescribing-and-support-governments-shifts-to-prevention-and-community/    Tackling overprescribing report: https://thehealthinnovationnetwork.co.uk//wp-content/uploads/2025/02/Health-Innovation-Network-Polypharmacy-Guide-Feb-2025.pdf    GP Evidence: (https://gpevidence.org/)   Please subscribe to the DTB podcast to get episodes automatically downloaded to your mobile device and computer. Also, please consider leaving us a review or a comment on the DTB Podcast iTunes podcast page. If you want to contact us please email dtb@bmj.com. Thank you for listening.

N Engl J Med 2019;381:1411-1421Background Percutaneous coronary intervention (PCI) had been clearly established as the standard of care for ST elevation myocardial infarction. Yet many patients taken for PCI have multiple lesions in addition to the culprit. The benefit of routinely treating additional significant lesions has been unclear, with previous smaller trials showing reductions in composite outcomes primarily driven by reduced revascularization rates.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.The COMPLETE (Complete vs Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI) trial investigated whether performing percutaneous coronary intervention (PCI) on non-culprit lesions reduces cardiovascular risk in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease.Patients The trial enrolled 4,041 patients from 140 centers in 31 countries between February 2013 and March 2017. Eligible patients had STEMI with successful culprit-lesion PCI and at least one non-culprit coronary artery lesion with ≥70% stenosis (or 50-69% stenosis with FFR ≤0.80) in a vessel ≥2.5mm in diameter. Patients were randomized within 72 hours after successful culprit-lesion PCI. Exclusion criteria included planned surgical revascularization and previous coronary bypass surgery.Baseline Characteristics The mean age was approximately 62 years, with about 80% being male. Approximately 19% had diabetes, 8% had previous MI, and 7% had previous PCI. Over 90% of patients underwent primary PCI (vs. pharmacoinvasive or rescue PCI), with 80% using radial access.The groups were well-balanced, with similar SYNTAX scores at baseline and similar culprit and non-culprit lesion characteristics. About 76% had one residual diseased vessel and 24% had two or more. Guideline directed medical therapy was robust and balanced, including more than 99% on dual antiplatelet therapy, 98% on statins, 88% on beta blocker, and 85% on ACEi or ARB.In patients in the complete revascularization group designated for non-culprit PCI during index hospitalization, the mean time to PCI was 1 day. In the group designated for non-culprit PCI after discharge, the mean time was 23 days.Trial procedures Patients were randomized to complete revascularization (n=2,016) or culprit-lesion-only PCI (n=2,025). In the complete revascularization group, investigators specified before randomization whether non-culprit PCI would occur during index hospitalization or after discharge (within 45 days).Everolimus-eluting stents were recommended for all procedures. Both groups received guideline-based medical therapy including dual antiplatelet therapy with aspirin and ticagrelor for at least one year.Endpoints The first coprimary outcome was cardiovascular death or new myocardial infarction. The second coprimary outcome was cardiovascular death, myocardial infarction, or ischemia-driven revascularization. Secondary outcomes included individual components of the composite outcomes, all-cause mortality, and safety outcomes like major bleeding, stroke, and stent thrombosis.Trialists estimated that a sample of 4000 patients would give 80% power to detect a 22% lower risk of the composite of cardiovascular death or myocardial infarction in the complete-revascularization group than in the culprit-lesion-only PCI group, assuming an event rate of 5% per year in the culprit-lesion-only PCI group. The first coprimary outcome was tested at a P value of 0.045 and the second at a P value of 0.0119.The co-primary endpoints were analyzed according to the time to first event approach. Confidence intervals for secondary and exploratory efficacy outcomes were not adjusted for multiple comparisons, and therefore inferences drawn from these intervals may not be reproducible.Results Over a median follow-up of 36.2 months, the first coprimary outcome occurred in 7.8% of the complete-revascularization group versus 10.5% of the culprit-lesion-only group (hazard ratio 0.74, 95% CI: 0.60-0.91; p= 0.004). Benefit was driven by reduced myocardial infarction rates (5.4% vs 7.9%) while cardiovascular death rates were similar (2.9% vs 3.2%).The second coprimary outcome was also reduced with complete revascularization (8.9% versus 16.7%, HR: 0.51, 95% CI: 0.43-0.61; p

We're back, after a brief hiatus! Today we talk about duration of therapy for bacteremia, Factor XI inhibition for atrial fibrillation, whether to stop ACEi or ARB before elective surgery, and whether GLP-1 agonists are beneficial in heart failure with preserved ejection fraction. Go to minute 7:30 to skip the banter. 7 vs 14 Days of Antibiotics for Bacteremia (BALANCE)Abelacimab vs Rivaroxaban for Atrial Fibrillation (AZALEA-TIMI-71)Asenduxian vs Apixaban for Atrial Fibrillation (OCEANIC-AF)ACEi or ARB Discontinuation Before Surgery (STOP or NOT)Tirzepatide for HFpEF and Obesity (SUMMIT)Music from Uppbeat (free for Creators!):https://uppbeat.io/t/soundroll/dopeLicense code: NP8HLP5WKGKXFW2R

The draft order:Sophia AmbrusoNayan AroraSwapnil HiremathAC GomezJoel TopfEditor Nayan AroraShow NotesPrevious drafts:2021 KDIGO Hypertension —Joel, Sophia, Swap, Nayan, Josh2021 ASN Kidney Week Draft—Joel, Sophia, Swap, Nayan, Jennie2022 The ISPD Peritonitis Guideline— Joel, Sophia, Swap, Nayan2022 ASN Kidney Week Draft—Joel, Sophia, Swap, Nayan2023 ASN Kidney Week Draft—Joel, Sophia, Swap, Nayan, AC, Josh2024 KDIGO CKD Clinical Practice Guideline —Joel, Sophia, Swap, Nayan, Josh, ACThe guidelineThe NephJC discussion Part 1 | Part 2First RoundSophia's Pick 3.7.1 We recommend treating patients with type 2 diabetes (T2D), CKD, and an eGFR ≥20 ml/min per 1.73 m2 with an SGLT2i (1A).Not Nayan's Pick 3.7.3: We suggest treating adults with eGFR 20 to 45 ml/min per 1.73 m2 with urine ACR

Chronic cough causes explained, looking at the differential diagnosis of a chronic cough as well as treatment options. Includes red flag symptoms associated with chronic cough.Consider subscribing on YouTube (if you found any of the info useful!): https://www.youtube.com/channel/UCRks8wB6vgz0E7buP0L_5RQ?sub_confirmation=1Patreon: https://www.patreon.com/rhesusmedicineBuy Us A Coffee!: https://www.buymeacoffee.com/rhesusmedicineTimestamps:0:00 What is a cough?0:30 Acute vs Chronic Cough1:38 Causes of a Chronic Cough 4:11 Chronic Cough Red Flags5:25 Chronic Cough TreatmentReferencesClinical Knowledge Summaries (2023) - “Cough”. Available at https://cks.nice.org.uk/topics/cough/Parker, S, M - British Thoracic Society (2023) - “British Thoracic Society Clinical Statement on chronic cough in adults**”.** Available at https://thorax.bmj.com/content/78/Suppl_6/s3Pinto, B (2020) “ACEI-induced cough: A review of current evidence and its practical implications for optimal CV risk reduction**”.** Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670268/Please remember this podcast and all content from Rhesus Medicine is meant for educational purposes only and should not be used as a guide to diagnose or to treat. Please consult a healthcare professional for medical advice. 

Episode 174: GERD in AdultsCommon and atypical symptoms are presented. Pathophysiology, diagnosis, and management are discussed. H. pylori's role is discussed during this episode. Written by Jacquelyn Garcia MS4 Ross University School of Medicine. Comments by Hector Arreaza, MD.You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.Definitions: Gastroesophageal reflux (GER): occasional backflow of stomach acid into the esophagus. It's a common physiological process that happens to many people, especially after meals. Occurs less than twice a week. Associated with mild and temporary symptoms such as heartburn or regurgitation. Gastroesophageal reflux disease (GERD): a chronic and more severe form of GER. It occurs when acid reflux happens frequently, typically more than twice a week, and/or causes esophageal injury/complications. -Non-erosive reflux disease (NERD)= GER without evidence of esophageal injury on endoscopy. -Erosive reflux disease (ERD)= GER with evidence of esophageal injury on endoscopy.AFP Journal, January 2024: “Nonerosive GERD does not increase the likelihood of esophageal cancer. However, erosive GERD is associated with a doubled, but still low, risk of developing cancer, with the likelihood increasing over time.”Pathophysiology:The main pathophysiology behind GERD is lower esophageal sphincter (LES) dysfunction which can occur due to the following:-LES Pressure: The LES is a muscular ring at the junction of the esophagus and stomach. It normally maintains a high-pressure zone to prevent reflux. In GERD, the intragastric pressure is higher than the pressure created by the LES. The tone of the LES can be reduced by caffeine, nitroglycerin, and scleroderma. -Transient LES Relaxations (TLESRs): These are normal relaxations of the LES that occur independently of swallowing. In GERD, these relaxations are more frequent or prolonged, allowing acid to reflux into the esophagus.-Anatomic abnormalities: A hiatal hernia occurs when a portion of the stomach protrudes through the diaphragm into the chest cavity. This disrupts the normal anatomy of the gastroesophageal junction, reducing the pressure barrier and promoting reflux.Epidemiology: It affects 10-20% of adults in Western cultures and less than 5% in Asia. Prevalence in the US ranges from 18.1% to 27.8% with a slightly higher rate in men. Risk factors: -Obesity, pregnancy, scleroderma, hiatal hernia; smoking, caffeine, alcohol, stress, fatty/fried/spicy foods. Spicy foods can be a challenge in some cultures (e.g. Mexican and Indian.) Sometimes, patients may ask for “something” to stop GERD but all they may need is dietary modification. -Medications: -aspirin, ibuprofen, clindamycin, tetracycline, bisphosphonates (irritate the esophagus and cause heartburn pain similar to GERD) -anticholinergics, TCA's, CCB's, ACEi, statins, benzodiazepines, theophylline, opioids, progesterone (increase acid reflux and worsen GERD)Clinical features: Typical symptoms: -heartburn (burning retrosternal pain) -regurgitation (acidic stomach contents)Atypical symptoms: -chest pain (can mimic angina pectoris, squeezing/burning substernal, radiates to back/neck/jaw/arm) -water brash (hypersalivation)-globus sensation (lump in throat)-nausea -belching-bloating Alarm features in GERD: -dysphagia-odynophagia (pain with swallowing)-new onset of dyspepsia in ≥60yo -weight loss-GI bleeding-vomiting-anemia Diagnosis: -There is no gold standard test -Patient with typical symptoms: diagnosis can be based on clinical symptoms alone -Patient with atypical symptoms: these symptoms can be seen in GERD but are not sufficient for diagnosis of GERD in the absence of typical symptoms. Need to rule out other disorders before associating the symptoms with GERD. (ex: chest pain r/o other causes such as MI with ECG) -Patient with alarm features: refer to GI for upper GI endoscopy. Complications: -Esophagitis: Erosive reflux disease (ERD) = GER with evidence of esophageal distal injury on endoscopy; in untreated GERD 30% have esophagitis. -Iron deficiency anemia: due to mucosal ulcerations -> chronic bleeding.-Esophageal stricture: narrowing near GE junction, solid food dysphagia.-Barrett Esophagus: intestinal metaplasia of esophagus due to chronic GERD (stratified squamous epithelium replaced by columnar epithelium)-Risk factors: GERD for 5-10 years, >50yo, males, obesity, Caucasian, Tobacco use, family history                 -Predisposes to esophageal adenocarcinoma Role of H. pylori.Sometimes we tend to think that H. pylori is the cause of GERD. “H. pylori infection appears to protect the esophagus from gastroesophageal reflux disease, Barrett's esophagus, dysplasia in Barrett's esophagus, and esophageal adenocarcinoma, perhaps by causing chronic gastritis that interferes with acid production.”It is unclear whether long-term use of PPIs heightens the risk of atrophic gastritis in patients with H. pylori. Consequently, routine screening for H. pylori infection and empiric eradication of H. pylori are NOT advised for patients with GERD. However, if H. pylori is diagnosed in the setting of GERD, eradication of H. pylori has been associated with an improvement of symptoms in patients with antral-predominant gastritis. Treatment: Two categories: Mild/intermittent symptoms (

N Engl J Med 2024;390:1372-1381Background: Beta-blockers are prescribed to the majority of patients with acute myocardial infarction. The bulk of evidence supporting this practice comes from trials published in the 1980s - BHAT and ISIS-I. Since the publication of these seminal trials, the care of patients with acute myocardial infarction has significantly changed with improvement in antiplatelet therapy, the addition of high-intensity statins and renin–angiotensin–aldosterone system antagonists in addition to early revascularization for STEMI patients. Furthermore, myocardial injury is now detected based on high-sensitivity troponin assays which can detect smaller myocardial infarctions. Therefore, there is a lack of evidence whether beta-blockers provide benefit for patients with acute myocardial infarction in the current era.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.The Randomized Evaluation of Decreased Usage of Beta-Blockers after Acute Myocardial Infarction (REDUCE-AMI) trial sought to assess whether long-term oral beta-blocker treatment improves outcomes in patients with acute myocardial infarction and preserved left ventricular ejection fraction.Patients: Eligible patients were adults, 1 to 7 days after myocardial infarction who underwent coronary angiography and echocardiography. Patients were required to have obstructive coronary artery disease on coronary angiography defined as stenosis of ≥50%, a fractional flow reserve of ≤0.80, or an instantaneous wave-free ratio of ≤0.89 at any time point before randomization. Left ventricular Ejection fraction on echocardiogram had to be ≥50%. Patients were excluded if they had contraindications to beta-blockers or if the treating physician determined that treatment with beta-blockers is indicated for other conditions.Baseline characteristics: The trial randomized 2,508 patients to the beta-blockers group and 2,512 patients to the control group. The average age of patients was 65 years with 78% being men. About 20% were current smokers, 46% had hypertension, 14% had diabetes, 7% had prior myocardial infarction and < 1% had prior heart failure.The index event was STEMI in 35% of the patients. About 96% underwent percutaneous coronary intervention. The median heart rate was 74 bpm and the median systolic blood pressure was 151 mm Hg.Medications at discharge included aspirin in 97% of the patients, P2Y12 inhibitors in 96%, ACEi or ARBs in 80% and statins in 99%.Procedures: Patients were randomized 1:1 to receive metoprolol succinate (first choice), bisoprolol (second choice) or no beta-blockers. The target doses were at least 100 mg daily for metoprolol succinate and at least 5 mg daily for bisoprolol. Patients in the control group were discouraged from using beta-blockers; they did not receive placebo. If a patient was on beta-blocker therapy at the time of enrollment and was randomly assigned to the no–beta-blocker group, the beta-blocker had to tapered off over a period of 2 to 4 weeks.Endpoints: The primary end point was a composite of death from any cause or new myocardial infarction. Secondary end points were death from any cause, death from cardiovascular causes, myocardial infarction, hospitalization for atrial fibrillation as primary diagnosis, and heart failure hospitalization. There were three safety endpoints: 1- Hospitalization for bradycardia, second- or third-degree atrioventricular block, hypotension, syncope, or implantation of a pacemaker, 2- hospitalization for asthma or chronic obstructive pulmonary disease as a primary diagnosis and 3- hospitalization for stroke.Data on clinical end points were not centrally adjudicated but rather obtained from the SWEDEHEART registry and the Swedish Population Registry.Statistical analysis was performed based on the intention-to-treat principle. Before trial initiation, the estimated event rate in the control group was 7.2%/ year and at least 16.7% lower event rate in the beta-blocker group was considered clinically meaningful. During the trial, the actual event rate in control group was 3%/ year. Given this event rate, a 25% lower event rate in the beta-blocker group was considered clinically meaningful. A total of 379 primary end point events were needed in order to have 80% power at a two-sided alpha of 0.05, to detect the 25% lower event rate with beta-blockers. The estimated number of patients needed was about 5,000.Results: Among the patients who attended the SWEDEHEART registry, 1500/1831 (81.9%) of the beta-blocker group were still taking beta-blockers after 11 to 13 months; compared to 269/ 1886 (14.3%) in the no beta-blocker group.After a median follow up time of 3.5 years, beta-blockers did not the reduce the composite primary endpoint compared to no beta-blockers (7.9% vs 8.3%, HR: 0.96; 95% CI, 0.79 - 1.16; p= 0.64). There were no significant differences in death from any cause (3.9% vs 4.1%), death from cardiovascular causes (1.5% vs 1.3%), myocardial infarction (4.5% vs 4.7%), hospitalization for atrial fibrillation (1.1% vs 1.4%) or hospitalization for heart failure (0.8% vs 0.9%).Safety endpoints were also not significantly different between both groups; 3.4% vs 3.2% for the bradyarrhythmia, syncope or hypotension endpoint, 0.6% in both groups for the hospitalization for asthma or COPD endpoint and 1.4% vs 1.8% for hospitalization for stroke.There were no significant subgroup interactions.Conclusion: In patients with acute myocardial infarction who underwent coronary angiography and had preserved left ventricular systolic function, treatment with beta-blockers did not improve outcomes over a 3.5-year follow-up. Events were infrequent in the trial; 1.4% for cardiovascular death, 4.6% for recurrent myocardial infarction and 0.8% for hospitalization for heart failure. The low event rate in this population in the current era makes it difficult to demonstrate additional benefit with more therapies.The open-label design of the study may have introduced performance bias; however, this bias is expected to favor beta-blockers given the superiority design of the study. Another limitation, as noted by the authors, is that outcomes were obtained from the SWEDEHEART registry and the Swedish Population Registry and were not centrally adjudicated. However, this is expected to affect both groups equally.We believe the divergent results between this trial and older beta-blocker trials in myocardial infarction patients such as BHAT and ISIS-1 which were published in the 1980s, is due to the significant improvement in the management of acute myocardial infarction over time including improved medical therapy in addition to early revascularization for STEMI patients. This improved patient care has led to significantly lower mortality rates over time. For instance, all-cause death in the control arm of REDUCE-AMI is significantly lower than that of BHAT and ISIS-1, at 4.1% vs 9.8% and 11.9%, respectively. This is despite REDUCE-AMI having a longer follow-up period of 3.5 years compared to 2.1 years and 1 year in the earlier trials.In conclusion, this study does not provide evidence that beta-blockers improve outcomes for patients with acute myocardial infarction and preserved ejection fraction in the contemporary era.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Acei Martin joins the show to share her experiences working as the stunt performer who doubled McKenna Grace for Ghostbusters Frozen Empire's NYC filming unit. Catch up on this week's headlines and then listen in as Acei tells tales of portraying Phoebe Spengler during the practical driving and gunners seat action sequences in the movie's opening moments!  Help support Acei's brother Carter's struggle with Amplified Musculoskeletal Pain Syndrome by donating to their GoFundMe: https://www.gofundme.com/f/support-carters-battle-with-amps   Special Thanks & Credits Logo / Cover Art - Brendan Pearce, Badoochi Studios, @badoochistudios Theme Song - "Ghostbusters" by MAGNAVOX

N Engl J Med 2012;367:1297-1309Background: In patients with acute coronary syndrome, clinical guidelines recommend early angiography particularly in those deemed moderate to high risk. However, a proportion of patients do not undergo revascularization, and these patients have poorer outcomes compared to those who do undergo revascularization.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.The TRITON-TIMI 38 trial demonstrated that prasugrel, when compared to clopidogrel, reduces ischemic events in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). Notably, in the TRITON-TIMI 38 trial, 99% of the patients underwent PCI at the time of randomization.Expanding upon the findings of TRITON-TIMI 38, the TRILOGY ACS trial sought to test the hypothesis that aspirin plus prasugrel is superior to aspirin plus clopidogrel in patients with acute coronary syndrome, without ST segment elevation, who are managed medically without revascularization.Patients: Patients were enrolled if they had unstable angina or non-ST elevation myocardial infarction and were treated medically without revascularization, within 10 days of the index event. Patients with non-ST elevation myocardial infarction had elevated cardiac biomarkers. Patients with unstable angina had ST-segment depression of more than 1 mm in two or more electrocardiographic leads and negative cardiac biomarkers. Patients had to have one of the following: age of 60 years or older, diabetes mellitus, prior myocardial infarction or prior revascularization with either PCI or coronary-artery bypass grafting (CABG). Main exclusion criteria were history of stroke or TIA (this group had net harm with prasugrel in TRITON-TIMI 38), renal failure requiring dialysis and patients taking oral anticoagulants.Baseline characteristics: The trial enrolled 9,326 patients at 966 sites in 52 countries. The average age of patients was 66 years, with 78% were below 75 years old, and 61% were men. About 70% of the patients had non-ST elevation myocardial infraction as their index event. The average GRACE score was 122. About 82% had hypertension, 59% had hyperlipidemia, 38% had diabetes, 43% had prior myocardial infarction and 20% were current or recent smokers. The majority of patients were stable, with 88% classified as Killip class I.Angiography before randomization was performed in 41% of the patients. Medications at randomization included beta-blockers in 78% of the patients, ACEi or ARB in 75%, statins in 83% and proton pump inhibitors in 25%.Procedures: The trial was conducted as double-blind double-dummy study. Patients who underwent randomization within 72 hours after the first medical contact received a loading dose of 30mg of prasugrel followed by 10mg daily. The maintenance dose of prasugrel was 5mg daily for patients aged 75 years or older or patients who weighed less than 60 kg. Patients who underwent randomization after 72 hours of the first medical contact received open label clopidogrel before randomization and the maintenance study drug after randomization. Clopidogrel was given as a loading dose of 300mg followed by a maintenance dose of 75mg daily. Aspirin was given in all patients and the recommended dose was 100mg per day or less. Study drugs were given for a minimum of 6 months and a maximum of 30 months.Endpoints: The primary efficacy endpoint was a composite of death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke among patients < 75 years old. Safety endpoints were bleeding not related to CABG based on Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) criteria for severe or life-threatening bleeding and Thrombolysis in Myocardial Infarction (TIMI) criteria for major bleeding, and neoplasms.Analysis was performed based on the intention-to-treat principle. The trial was event-driven. To ensure 90% power to detect 22% relative risk reduction of prasugrel over clopidogrel with a two-sided alpha of 5%, a total of 688 patients,

JAMA. 2006;295(13):1519-1530Background Previous trials demonstrated that aspirin and thrombolytic therapy improve prognosis in patients with ST elevation myocardial infarction (STEMI). The addition of heparin to aspirin and thrombolysis did not improve outcomes in patients with STEMI (see GISSI-2 trial). Fondaparinux, a synthetic pentasaccharide that inhibits factor Xa, was tested in OAISIS-5, and was found to be noninferior to enoxaparin in patients with acute coronary syndrome (without STEMI) and was associated with less bleeding.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.The Sixth Organization for the Assessment of Strategies for Ischemic Syndromes (OASIS-6) trial sought to test the hypothesis that fondaparinux is superior to the standard of care in patients with STEMI.Patients Patients were enrolled if they had STEMI and were within 24 hours from onset of symptoms. The time window was later shortened to 12 hours. Patients at high risk for bleeding (this was not clearly defined), receiving oral anticoagulants or who had serum creatinine levels greater than 3.0 mg/dL were excluded.Baseline characteristics The trial enrolled 12,092 patients. The average age of patients was 62 years and 72% were men. The mean heart rate and systolic blood pressure on admission were 76 bpm and 134 mm Hg, respectively. About half had hypertension, 18% had diabetes, 14% had heart failure, 13% had prior myocardial infarction, 7% had prior stroke, and 4% had prior coronary artery bypass graft or percutaneous coronary intervention (PCI). About 58% were active or former smokers. In-hospital medications, after randomization, included aspirin in 97% of the patients, beta-blockers in 84%, ACEi or ARB in 80%, clopidogrel or ticlopidine in 58% and glycoprotein IIb/IIIa receptor antagonist in 16%.During the index hospitalization, coronary angiography was performed in about 44% of the patients but primary percutaneous coronary intervention was performed in 31%. Thrombolytic therapy was given in 45% of the patients.Procedures OASIS-6 was a randomized double-blind trial. Patients were divided into two groups based on the investigator's judgment - Group 1: No indication for heparin and group 2: Indication for heparin, thrombolysis or PCI. Patients in group 1 received fondaparinux 2.5 mg subcutaneously once daily or matching placebo. Patients in group 2 received fondaparinux 2.5 mg subcutaneously once daily + heparin placebo or heparin + fondaparinux placebo. For patients who received heparin, an initial bolus of 60 IU/kg was given followed by an infusion of 12 IU/kg per hour for 24-48 hours. A placebo bolus and continuous infusion were used in the fondaparinux group, in group 2. Fondaparinux was given for 8 days or until hospital discharge, or whichever came first. To maintain blinding, all patients in group 2 had aPTT checked and a central system produced either a real or sham value.Endpoints The primary efficacy endpoint was all-cause death or reinfarction at 30 days. Secondary endpoint was the primary endpoint at 9 days, and at 3 and 6 months (only half the patients were followed for 6 months). Safety endpoints included major and minor bleeding. Based on an event rate of 8% at 9 days, the estimated sample size to have 90% power to detect 20% relative risk reduction with fondaparinux was 10,000. However, after 8,000 patients were enrolled, the event rate was lower than expected so the sample size was increased to 12,000 and the primary endpoint was changed to 30 days.Results The study assigned 6,036 patients to the fondaparinux group and 6,056 to control group. The fondaparinux group included 2,823 patients from group 1 and 3,213 patients in group 2. The control group included 2,835 patients in group 1 and 3,221 patients in group 2.Death or reinfarction was lower with fondaparinux at 9 days (7.4% vs. 8.9%, HR: 0.83, 95% CI: 0.73 – 0.94; p= 0.003), at 30-days (9.7% vs. 11.2%, HR: 0.86, 95% CI: 0.77 – 0.96; p= 0.008) and at 3-6 months (13.4% vs. 14.8%, HR: 0.88, 95% CI: 0.79 – 0.97; p= 0.008). Death was significantly lower with fondaparinux at 9 days (6.1% vs 7.0%; p= 0.04), 30-days (7.8% vs 8.9%; p= 0.03) and 3-6 months (10.5% vs 11.6%; p= 0.03).Severe hemorrhage was not significantly different between both treatment arms (1.0% in the fondaparinux group and 1.3% in the control group, HR: 0.77, 95%: 0.55 –1.08; p= 0.13).The beneficial effect of fondaparinux on the primary outcome was larger for group 1 at 9 days and 30 days. The absolute risk reduction in the primary endpoint with fondaparinux in group 1 vs group 2 was 2.6% vs 0.5% at 9 days and 2.8% vs. 0.4% at 30-days. Another important subgroup is patients who underwent PCI where fondaparinux had no benefit.During the initial hospitalization, 1898 patients allocated to receive UFH or placebo and 1890 patients allocated to receive fondaparinux underwent any primary PCI in the hospital. Death and MI did not differ significantly at 30 days. In patients who had coronary angiography, fondaparinux was associated with guiding catheter-related thrombosis, (0 vs 22; P 

N Engl J Med 2006; 354:1464-1476Background: Prior studies showed that combined antiplatelets and anticoagulants reduce ischemic events in patients with acute coronary syndrome but increases the risk of bleeding. We saw this in the FRISC trial where low-molecular-weight heparin plus aspirin reduced the primary endpoint of death or nonfatal myocardial infarction compared to placebo at 6 days but also increased minor bleeding events (8.2% vs 0.3%).Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Fondaparinux is a synthetic pentasaccharide that inhibits factor Xa and has a long half-life (17 – 21 hours). In contrast, low-molecular-weight heparin is biologic and has a half-life of 3 - 6 hours.Pilot studies showed that fondaparinux may be as effective as enoxaparin in patients with acute coronary syndrome. The Fifth Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS-5) trial sought to test the hypothesis that in patients with unstable angina or NSTEMI, fondaparinux would be noninferior to enoxaparin in reducing ischemic events but would be associated with less bleeding.Patients: Patients were enrolled if they had at least two of the following criteria: at least 60 years of age, elevated cardiac biomarkers (troponin or creatine kinase MB) or ischemic EKG changes but not ST elevation. Patients were excluded if they had contraindication to low-molecular-weight heparin, recent hemorrhagic stroke or serum creatine of 3 mg/dl or more.Baseline characteristics: The trial enrolled 20,078 patients. The average age of patients was 67 years with 62% being men. About 45% had unstable angina and the rest had NSTEMI. Prior myocardial infarction was present in 26% of the patients, stroke in 6%, heart failure in 14%, hypertension in 67% and diabetes in 25%. About half the patients were active or former smokers.After randomization, about 98% of the patients were on aspirin, 67% were on clopidogrel or ticlopidine, 75% were on ACEi or ARB and 87% were on beta-blockers.During first hospital stay, coronary angiography was performed in 63% of the patients but percutaneous coronary intervention was performed in only 34% and this was similar between both treatment groups. Coronary artery bypass graft (CABG) was performed in 9% in the enoxaparin group and 9.6% in the fondaparinux group.Procedures: The trial was a double-blind, double-dummy trial. Patients were randomly assigned within 24 hours of onset of symptoms to receive fondaparinux at a dose of 2.5 mg once daily plus placebo twice daily or enoxaparin at a dose of 1 mg/ kg twice daily plus placebo once daily. All medications and placebo were administered using subcutaneous injection. Fondaparinux was given until hospital discharge or up to 8 days (whichever occurred first).  Enoxaparin was given for 2 – 8 days. Coronary angiogram was permitted at any time.Endpoints: The primary efficacy endpoint was a composite endpoint that included death, myocardial infarction or refractory ischemia at 9 days. The primary safety endpoint was major bleeding. Secondary endpoint included the primary endpoint and its individual components at 30 days and end of the study (up to 180 days).Based on an expected incidence of 8% at 9 days for the primary endpoint and a noninferiority margin of 1.185 for a one-sided alpha level of 2.5%, the estimated sample size was 16,000. However, a blinded review after the first 4,000 patients were enrolled showed a lower than expected event rate. Therefore, the sample size was increased to 20,000 patients.Results: The study randomized 10,057 patients to receive fondaparinux and 10,021 to receive enoxaparin. At 9 days, the primary composite end point occurred in 5.8% patients assigned to fondaparinux and 5.7% patients assigned to enoxaparin (HR: 1.01, 95% CI: 0.90 - 1.13; p= 0.007 for non-inferiority). All components of the primary endpoint were also similar between both treatment arms at 9 days.At 30 and 180 days, there was no significant difference in the composite primary endpoint between both treatment arms. However, death (secondary endpoint) was significantly lower with fondaparinux at 30 days (2.9% vs 3.5%; p= 0.02) and the difference persistent at 180 days (5.8% vs 6.5%; p= 0.05).Major bleeding at 9 days was significantly lower with fondaparinux (2.2% vs. 4.1%; HR: 0.52,  95% CI: 0.44 - 0.61; p

NEJM 1995;333:1670-6.Background Up to this point in history, a series of trials had been conducted using ACEi's in post-MI patients. A small to moderate short-term benefit had been shown when the drugs were started immediately (GISSI-3 and ISIS-4) and much greater long-term benefits were demonstrated when the drugs were started 5-11 days, on average, following AMI in patients with LV dysfunction and congestive heart failure (SAVE and AIRE).The SAVE and AIRE trials, however, were more selective and it was not clear how representative they were among all potentially eligible patients. Thus, TRACE authors sought to re-test the hypotheses tested in SAVE and AIRE with a focus on generalizability of trial procedures and results. Specifically, the Trandolapril Cardiac Evaluation Study (TRACE) sought to test the hypothesis that trandolapril would reduce all-cause mortality in post-MI patients with LV dysfunction when used in the majority of consecutively screened, potentially eligible patients.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients Consecutive patients ≥18 years of age who were hospitalized with a confirmed AMI were screened between day 2 and 6 after the onset of symptoms. All screen eligible patients underwent echocardiography and those with a wall motion index of ≤1.2, which corresponds to an EF ≤35%, were considered for enrollment. The key exclusion criteria included an absolute or relative contraindication to an ACEi or a definite need for an ACEi, severe uncontrolled diabetes, a serum sodium 2.3 mg/dl.Baseline characteristics The average age of patients was 68 years and 72% were men. Approximately one third of patients had a prior MI, 13% had diabetes, 23% had hypertension and smoking status was not listed. The average wall motion index was 1.0. Two thirds of patients had a Q wave MI (anterior 47% and inferior 19%). The mean time to randomization was 4.5 days. Forty-five percent of patients received thrombolysis. The average blood pressure and heart rate were 120/70 mmHg and 76 beats per minute, respectively. At the time of randomization 16% of patients were receiving a beta blocker and 28% digoxin. Before randomization, 60% of patients had been classified as Killip class ≥2 and at the time of randomization it was 21%.A total of 6,676 consecutive patients experienced an AMI of whom 2,606 had a wall motion index of ≤1.2. There was an inverse relationship between wall motion index and mortality. In patients with scores ≥1.3, 40% had signs of CHF and the 1-year mortality rate was 12%. Among patients with scores ≤1.2, 74% had signs of CHF and the 1-year mortality was 34%.Of the 2,606 eligible patients, 859 (33%) were excluded. The most common reasons for exclusion included need for mandatory ACE inhibition [6%], cardiogenic shock [4%], death during screening [3%], renal failure or a single kidney [2%], intolerance of the test dose of trandolapril [1%], lack of consent [8%], or other reasons [8%].Altogether, 1,749 (67%) of patients with a wall motion index score ≤1.2 were enrolled.Procedures Eligible patients were given a test dose of 0.5 mg of trandolapril, which led to the exclusion of 1% of patients. These patients were not included in the ITT analysis. Double-blind medication was started between day 3 and day 7 after AMI. Patients were randomly assigned to receive 1 mg of trandolapril once daily or matching placebo. After two days, the dose was increased to 2 mg once daily. After four weeks, the dose was again increased, to 4 mg once daily. If the highest dose was not tolerated, patients could continue with a dose of 2 mg or 1 mg once daily, but the drug was withdrawn if a dose of 1 mg once daily was not tolerated.Outpatient visits were scheduled one and three months after the infarction, with subsequent visits every three months. Echocardiography was repeated after 3, 6, and 12 months.The original protocol specified that treatment would continue for at least 12 months. When the results of the SAVE study were published in 1992, showing no survival benefit until after almost one year of treatment with ACE inhibitors, the steering committee decided (without any knowledge of the results of the study) to extend the closing date to 24 months after the last random assignment.Endpoints The primary study endpoint was all-cause mortality. Secondary endpoints were death from a cardiovascular cause, sudden death, progression to severe heart failure, recurrent MI, and change in wall motion index.The investigators estimated they would need a sample size of 1,500 patients to detect a 25% relative reduction in the risk of death with 80% power and 1-sided alpha of 2.5%. This was based on an estimated death rate of 30% at 12 months in the placebo group; however, the steering committee increased the sample size to 1,860 patients to allow for the possibility of a lower-than-expected placebo mortality rate.In the spring of 1992 the overall mortality of randomized patients followed for 1 year was 24%. Inclusion of patients was therefore terminated at the end of June 1992 at the point where 1,749 patients had been randomized.Results The final analysis included 1,749 patients; 876 in the trandolapril group and 873 in the placebo group.Information on the percentage of patients discharged on various doses of the study drug are not provided.Compared to placebo, trandolapril significantly reduced all cause death by 22% [(35% vs 42%; 95 percent confidence interval, 0.67 to 0.91 p = 0.001)}. The mortality curves diverged early (Kaplan–Meier estimate of mortality at one month 9% vs 11%) and continued to diverge throughout the follow-up period. Trandolapril also significantly reduced secondary endpoints, including death from CV causes, sudden death, and progression to severe heart failure but it did not significantly reduce reinfarction.Examination of subgroups showed no evidence of treatment effect heterogeneity for all cause mortality, but again, similar to the SAVE and AIRE trials, the size of TRACE limits subgroup testing.Premature withdrawals from study drug, not including death, occurred in 37% of patients in the trandolapril group compared to 36% in the placebo group. The most common reason for withdrawal was need for treatment with an open-label ACEi and this occurred more in the placebo group. Withdrawal due to cough, hypotension and reduction in kidney function were rare in both groups but slightly more common in patients on trandolapril compared to placebo.Conclusions In the majority (67%) of consecutively screened patients with AMI complicated by left ventricular dysfunction, trandolapril significantly reduced death over at least 2 years of follow-up with a number needed to treat of approximately 14 patients. Results from TRACE strengthen support for ACEi in post-MI patients, and the trial has high external validity. It not only tested the intervention in two-thirds of potentially eligible patients but was highly transparent about why patients were excluded. A clinician looking to apply the procedures used in TRACE to the management of patients in clinical practice would not have to guess whether or not their patient would have been included. This is rare in clinical research and the investigators should be applauded for their efforts.Investigators studying ACEi in post-MI patients have triangulated the population of patients who benefit from this therapy. In our opinion, TRACE provides the final piece to the puzzle. There is no doubt about the clinical efficacy of these drugs in the overwhelming majority of post-MI patients and higher risk patients stand to benefit the most.Thank you for reading Cardiology Trial's Substack. This post is public so feel free to share it. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Two seminal trials of ACEi in patients with acute myocardial infarction complicated by heart failure or left ventricular systolic dysfunction. See https://cardiologytrials.substack.com for full details Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Lancet 1993;342:821-28.Background The Survival After Ventricular Enlargement (SAVE) trial demonstrated that administration of the angiotensin converting enzyme inhibitor (ACEi) captopril, following MI complicated by LV dysfunction (EF ≤40%) but without clinical heart failure significantly improved morbidity and mortality over 3.5 years of follow-up. Yet many post-MI patients at the time had clinical heart failure and this represented a vulnerable population of patients with significantly increased morbidity and mortality compared to those without clinical heart failure. The Acute Infarction Ramipril Efficacy (AIRE) trial sought to test the hypothesis that administration of Ramipril to patients with AMI complicated by acute congestive heart failure would reduce morbidity and mortality vs a placebo. Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients Eligible patients were 18 years of age or older with a definite AMI occurring 2 to 9 days prior to randomization with clinical evidence of congestive heart failure at any time after the index MI. While clinical evidence of heart failure was mandatory for study entry, it could be transient and not necessarily present at the time of randomization. Patients were excluded with NYHA IV heart failure (these patients would receive ACEi therapy regardless), heart failure of primary valvular or congenital etiology, or patients with any recognized contraindications to ACEi therapy were excluded.Baseline characteristics The average age of patients was 65 years and 74% were men. Approximately one quarter of patients had had a prior MI, 12% had diabetes, 30% had hypertension and smoking status was not listed. The ejection fraction of study participants was not systematically assessed as part of the study protocol. 62% had a Q wave MI and the predominant location was anterior. The mean time to randomization was 5 days. Approximately 60% of patients received thrombolysis. The average blood pressure and heart rate were not provided. At the time of randomization 22% of patients were receiving a beta blocker and 12% digoxin.Many more patients (52,019) were reviewed than ultimately enrolled (1,986). The main reasons for exclusion were no definitive MI (21,302) and no definite heart failure (16,989). The authors estimate that among eligible patients with a definitive MI and heart failure that approximately half were enrolled. Information on those enrolled versus not enrolled was not provided.Procedures Patients were initiated on Ramipril 2.5 mg twice daily or matching placebo for 2 days after which the dose was increased to 5 mg twice daily. If patients could not tolerate the 5 mg twice daily dose they were discharged on 2.5 mg twice daily. For patients who could not tolerate the 2.5 mg dose they were given 1.25 mg twice daily for 2 days with attempts to up-titrate to 2.5 mg and 5 mg at discharge. For patients that could not tolerate at least 2.5 mg twice daily at discharge they were NOT discharged on the 1.25 mg dose. These patients were withdrawn from study treatment but followed up at the prespecified visit intervals and were included in the intention-to-treat analysis.Outpatient visits were scheduled at 1 month and 3 months following discharge from the index hospitalization and every 3 months thereafter until study close. Monitoring of renal function and electrolytes was done at the discretion of study investigators based on their normal practice. During follow up patients could be started on any medication with exception of an ACEi.Endpoints The primary study endpoint was all-cause mortality. The secondary endpoint was time to first event including (death, progression to NYHA class 4 heart failure, reinfarction or stroke).The investigators estimated they would need a sample size of 2,000 patients to detect a 25% relative reduction in the risk of death with 80% power and 2-sided alpha of 5%. This was based on an estimated death rate of 20% at 15 months in the placebo group and 15% in the Ramipril group.Results 2,006 patients were recruited from 144 centers in 14 countries. However, 20 patients from 1 center were excluded from the final analysis due to inconsistencies in the data. According to investigators the exclusion of these patients did not meaningfully change the final results. The final analysis included 1,986 patients; 1004 in the Ramipril group and 982 in the placebo group.90% of study participants were discharged from the hospital on study drug. In the Ramipril group, 77% were on the 5 mg dose, 14% were on the 2.5 mg dose and 9% were on no therapy. In the placebo group, 86% were on the 5 mg dose, 7% on the 2.5 mg dose and 7% on no therapy.Patients were followed for an average of 15 months and only 1 was lost to follow-up. Compared to placebo, Ramipril significantly reduced all cause death by 27% (17% vs 23%; p = 0.002). Ramipril also significantly reduced the secondary composite endpoint of time to first validated event (including death, progression to severe heart failure, reinfarction or stroke) by 19% (28% vs 34%; p = 0.008). Differences in this composite endpoint were mainly driven by death and progression to severe heart failure.Examination of subgroups showed no evidence of treatment effect heterogeneity but again, similar to the SAVE trial, the size of the trial limits subgroup testing.Premature withdrawals from study drug, not including death, occurred in 352 patients in the Ramipril group compared to 318 in the placebo group. Intolerance to the drug was cited as a factor in 126 of the Ramipril withdrawals and 68 of the placebo withdrawals whereas progression to severe heart failure was cited in 58 Ramipril withdrawals and 92 placebo. Syncope was more common in Ramipril treated patients compared to placebo (2.4% vs 1.7%) and so was hypotension (4.2% vs 2.3%) but not renal failure (1.5% vs 1.2%).Conclusions In patients with AMI complicated by clinical congestive heart failure, Ramipril significantly reduced death over 1.3 years of follow-up with a number needed to treat of approximately 17 patients. Ramipril also significantly reduced a composite of events, which were mainly driven by death and progression to severe heart failure. Unlike the SAVE trial, which did not estimate a particular sample size for hypothesis testing, AIRE was specifically designed to test whether Ramipril would reduce death by 25% over 15 months and indeed, it did! Thus, results from AIRE not only support but add legitimacy to findings from SAVE.One perceived limitation of AIRE, particularly when viewed through a contemporary lens, is its lack of ejection fraction estimation. There should be no doubt that these were sick patients in whom, significant LV dysfunction would have been present in most. We base this claim on the observation that the death rate in AIRE at 1.3 years in the placebo group was nearly equal to SAVE at 3.5 years (23% vs 25%). This highlights that development of clinical heart failure (regardless of LV function) confers a worse prognosis than LV dysfunction without heart failure.In our opinion, the external validity of AIRE is high for a trial performed 30 years ago. The average start date for treatment was 5 days post MI complicated by clinical heart failure. This is longer than we would anticipate in contemporary practice by 2 or 3 days but not unreasonable, especially for post-MI patients with tenuous hemodynamics requiring intravenous diuretic therapy. Furthermore, the dose titration parameters and follow up schedule in AIRE can be approximated in clinical practice. Also, no obvious treatment effect heterogeneity was noted across important subgroups (e.g., age > vs < 65 years) but these analyses are limited due to the overall sample size. Finally, no strict limits were placed on blood pressure and heart rate at study entry.Thank you for reading Cardiology Trial's Substack. This post is public so feel free to share it. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

NEJM 1992;327:669-77 Background After a large heart attack, cardiac hemodynamics are altered, which leads to a series of changes in the heart muscle itself. The immediate consequence of a large heart attack is decreased myocardial contractility. This leads to a reduction in stroke volume and cardiac output. Compensatory mechanisms governed by the renin-angiotensin-aldosterone system and sympathetic nervous system become activated and may lead to ventricular dilation or “remodeling”, which has negative short and long-term consequence for the heart muscle.By the mid-1980's, angiotensin converting enzyme inhibitors (ACEi) were commonly used for patients with chronic systolic heart failure and laboratory work had shown they could improve ventricular remodeling, reduce heart failure and prolong survival in animal models of AMI. Several studies had also shown promise in humans but they were too small to test hypotheses involving hard clinical endpoints. The Survival and Ventricular Enlargement (SAVE) trial sought to test the hypothesis that administration of captopril to patients with AMI complicated by left ventricular dysfunction but who did not have overt heart failure requiring vasodilatory therapy would reduce morbidity and mortality over long-term follow-up.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients Eligible patients were between 21 to 80 years of age with a definite myocardial infarction occurring 3 to 16 days prior to randomization with a left ventricular ejection fraction (EF) ≤40%, measured by radionuclide ventriculography. Patients were excluded with relative contraindications to ACEi or if an ACEi was indicated for treatment of symptomatic congestive heart failure or systemic hypertension. Other exclusion criteria included serum creatinine >2.5 mg/dl, other conditions limiting survival (unspecified) or who had an unstable course following AMI (also unspecified).Baseline characteristics The average age of patients was 59 years and 82% were men. Approximately one third of patients had a prior MI, more than 20% had diabetes, 40% had hypertension and over 50% were current smokers. The average ejection fraction was 31% and over half of patients had an anterolateral Q wave MI. The mean time to randomization was 11 days. Prior to randomization approximately a third received thrombolysis, over 50% underwent coronary angiography, and approximately 25% underwent either percutaneous coronary angioplasty or coronary artery bypass surgery. At the time of randomization, the average blood pressure was 113/70 mmHg and heart rate was 78 beats per minute. Within 24 hours of randomization approximately one third of patients received a beta blocker and a quarter received digoxin.Procedures There was a mini run-in period where all 2,250 eligible patients were given a test dose of 6.25 mg of captopril. This led to exclusion of 19 patients (3 for ischemic discomfort and 16 for symptomatic hypotension).Patients received either captopril or placebo. The initial dose of the blinded study drug was 12.5 mg but could be administered at 6.25 mg to patients who had marked, yet asymptomatic, reduction in BP with the run-in dose. The target dose was 25 mg three times a day by the end of the in-hospital phase and was gradually increased to 50 mg three times a day unless side effects occurred. There was no prespecified level of blood pressure in the titration regimen.Outpatient visits were scheduled 2 weeks following randomization and then every 3 months during year 1 and every 4 months thereafter. Compliance with the study drug was assessed by pill count.Endpoints There were no prespecified hypothesis tests used to determine sample size. Prospectively defined measures of outcomes included all cause death, cardiovascular death, incidence of clinical congestive heart failure and first hospitalization for heart failure. Once the clinical endpoint committee was notified of a diagnosis of clinical heart failure the study medication was discontinued so open-label therapy with an ACEi could be started.Results 2,231 patients were included in the final analysis; 1116 in the placebo group and 1115 in the captopril group. The mean follow-up was 3.5 years. Blood pressure increased from baseline in both groups but to differing extents. At 3 months, BP was 125/77 in the placebo group compared to 119/74 in the captopril group. The average heart rate was 74 in both groups.Compared to placebo, captopril significantly reduced all cause death by 19% (20% vs 25%; p = 0.019) and cardiovascular death by 21% (17% vs 21%; p = 0.014). It also reduced clinical heart failure by 37% (11% vs 16%; p

Discussion of two landmark trials of ACEi and nitrates in acute coronary syndrome. ISIS-4 had also an arm for magnesium. The story of magnesium is very interesting!!! See https://cardiologytrials.substack.com/ for full details. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Happy to have you with us! Ring in the New Year with clinical updates around piperacillin-tazobactam vs cefepime in AKI, corticosteroids in severe CAP with a clinical trial and several meta-analyses, perioperative management of ACEI/ARBs, and AE in inpatient medicine. | 00.33 - Introduction | | 01.00 - ACORN trial [JAMA 2023] - In 2500 patients presenting to the ED with sepsis, there was no statistically significant difference in AKI or death @ 14 days with pip/tazo vs cefepime, but cefepime did cause a decrease in delirium or coma free days | | 01.55 - CAPE COD with Dequin et al. in France? trial [NEJM 2023] In 800 patients admitted to the ICU with severe CAP, hydrocortisone administration was associated with reduced death from any cause at 90 days and reduced need for intubation | 02.54 - PROSPERO [CHEST 2023] - Doesn't include Dequin's study. Concludes that there was a reduced incidence of intubation, but no reduced mortality. 03.26 - CID meta-analysis including the CAPE COD study by Dequin et al. [CID 2023] many studies similar to the PROSPERO study, but including Dequin et al. Therefore resulting in the conclusion of decreased mortality on top of reduced intubation. | 04.21 - POISE-3 - hypotension avoidant vs hypertension avoidant strategies in properties ACEI/ARB management [ AIM 2023] | | 05.58 - Adverse events in Massachusetts hospitals. What can we focus on for the future? [NEJM 2023] | | 07.15 - Happy new year! | [The appearance of external hyperlinks does not constitute endorsements by UCSF of the linked websites, or the information, products, or services contained therein. UCSF does not exercise any editorial control over the information found therein, nor does UCSF make any representation of their accuracy or completeness. All information contained in this episode are the opinions of the respective speakers and not necessarily the views their respective institutions or UCSF, and is only provided for information purposes, not to diagnose or treat.] Music by Amit Apte. *Image by rawpixel.com on Freepik.*

1 Timotei 4:1–5 (Depărtarea de credință)1 Timotei 4:1-5 (VDCL)1 Duhul însă spune lămurit că în vremurile din urmă unii se vor lepăda de credință, luând aminte la duhuri amăgitoare și învățături de draci,2 care vorbesc minciuni în fățărnicie, înfierați în cugetul lor, ca și cu fierul roșu,3 oprind căsătorirea și poruncind a se feri de mâncări, pe care Dumnezeu le‐a făcut să fie luate cu mulțumiri de cei credincioși și care au cunoscut pe deplin adevărul.4 Pentru că orice făptură a lui Dumnezeu este bună și nimic nu este de lepădat dacă se ia cu mulțumiri;5 căci este sfințit prin Cuvântul lui Dumnezeu și rugăciune.Primele două versete din textul de mai sus afirmă că în vremurile din urmă unii oameni se vor lepăda de credință acordând atenție spiritelor înșelătoare și doctrinelor demonilor, fără să-și dea seama de acest lucru bineînțeles, și din ipocrizie vor vorbi minciuni, conștiința acestora fiind însemnată cu fierul roșu. Mulți creștini cred că lepădarea de credință din aceste verste se referă la pierderea mântuirii veșnice, pentru că ei interpretează duhurile înșelătoare și învățăturile demonilor ca păcate imorale care, în cele din urmă, îi vor face pe unii creștini autentici să-și piardă mântuirea. Însă, te invit să luăm lucrurile pe rând și să vedem mai întâi în ce constau aceste învățături greșite și apoi cine sunt acei „unii” care se vor lepăda de credință, la ce fel de credință se referă și ce înseamnă această îndepărtare.Înainte de toate, aș dori să menționez că verbul „a lepăda” din versetul 1 ales de traducerea Cornilescu pentru a transla cuvântul grecesc apostesontai (îndemnând îndepărtare sau distanțare) este unul mult prea sever care transmite ideea de renunțare definitivă și ireversibilă la credință, în deplină conștiență de cauză a persoanei. Exclude posibilitatea persoanei de a fi înșelată (vezi expresia duhuri amăgitoare din versetul 1) sau îndepărtarea să fie una temporară cu posibilitatea de revenire.  O traducere mai fidelă a acestui verset ar fi următoarea:1 Timotei 4:1-5 (BTF2015)1 Iar Duhul spune în mod clar că, în timpurile din urmă, unii se vor depărta de credință, dând atenție duhurilor amăgitoare și doctrinelor dracilor.Versetele 3 și 4 descriu unele dintre lucrurile și doctrinele pe care acești oameni le promovează și anume: interzicerea căsătoriei și abținerea de la anumite mâncăruri. Lucrurile relatate aici nu sunt păcate imorale și plăceri trupești în care oamenilor le place de obicei să  trăiască, ci mai degrabă „alte căi aparent bune” și ascetice de a dobândi neprihănirea. Ele sunt învățături și doctrine, dar nu păcate.Aceste învățături sunt îmbrăcate într-o înfățișare de sfințenie ceea ce le face foarte subtile și înșelătoare. Judecând după natura lor, se pare că cei care le propagau, încercau să fie sfinți prin fapte în loc de credință. Ei credeau că sfințenia vine din respectarea strictă a unui set de reguli. Aceste doctrine par să se asemene cu Legea lui Moise și să fie de natură iudaică. Cine pot fi oare acești oameni? Din moment ce pasajul vorbește de o îndepărtare de credință înseamnă că acei oameni au avut contact la un moment dat cu învățătura curată a mântuirii numai prin credința în Cristos. Ei fie au fost atât de convinși încât au fost și născuți din nou, sau s-au alăturat doar bisericii pentru o vreme, însă nu au putut să renunțe pe deplin la Legea lui Moise și nu fuseseră născuți din nou niciodată. Pavel îi numește ipocriți și mincinoși din cauză că una predicau altora, însă ei făceau exact invers în viața lor privată, iar conștiința lor a ajuns să fie insensibilă datorită trăirii lor constante în acel stil de viață. Ei nu mai vedeau seriozitatea contradicției din viața lor din dorința de a apărea în fața oamenilor ca fiind religioși și sfinți. După cum zona în care un animal însemnat cu fierul roșu devine amorțită și insensibilă la durere, așa și conștiința acestor oameni se desensibilizase. Din această cauză, apostolul Pavel descrie conștiința lor ca fiind însemnată cu fierul roșu.E foarte posibil ca acei „unii” influențați de învățăturile iudeilor să fie chiar lideri (păstori și învățători) ai bisericii lui Cristos din Efes, din moment ce ereziile avea legătură cu doctrine care de obicei sunt predicate din față. Mai mult decât atât, în 1 Timotei 1:7, ei sunt descriși ca dorind să fie învățători ai Legii. Dacă aceștia erau născuți din nou, ei îl iubeau probabil pe Dumnezeu, erau mântuiți veșnic prin har, dar din când în când erau „mușcați” de auto-neprihănirea propagată de adepții Legii lui Moise și se concentrau în principal pe faptele lor bune pentru a-I plăcea lui Dumnezeu aici pe pământ, iar aceasta era din cauza lipsei de înțelegere și revelație. Ei nu erau încă pe deplin stabiliți în Cristos și în credința în adevăr în toate domeniile. Aceasta nu înseamnă că își pierduseră mântuirea veșnică, ci că în viața lor de zi cu zi, ei se bazau mai mult pe neprihănirea lor de sine pentru a atrage favoarea lui Dumnezeu, în loc să aplice aceeași credință simplă pe care au avut-o la momentul mântuirii. Așadar, depărtarea lor de credință nu era o cădere ireversibilă din credință, ci o îndepărtare temporară sau limitată doar la unele aspecte ale vieții lor de credință. La fel se întâmplă și în ziua de azi cu mulți creștini autentici din trupul lui Cristos care mai alunecă din când în când în neprihănire de sine sau nu au o credință deplină în adevăr în toate domeniile vieții lor. Pavel nu a avut în vedere aici pierderea mântuirii veșnice. O mulțime de creștini născuți din nou, care sunt încă legaliști și auto-neprihăniți, vor merge în continuare în rai.Din acest pasaj putem extrage și niște principii generale de credință. De exemplu, minciuna diavolului va avea întotdeauna ca rezultat o mântuire bazată pe fapte. Aceasta este atrăgătoare deoarece o religie orientată spre fapte bune pare impresionantă, sfântă și dreaptă pentru alții. Putem examina religie cu religie și vom observa că toate se bazează pe ceea ce faci sau nu faci. Se crede că, astfel, Dumnezeu este îmbunat în cerințele Lui, sau, cu alte cuvinte, lucrările omenești bune Îl temperează, Îl înduplecă pe Dumnezeu. Însă, toate aceste învățături sunt satanice și alimentate de demonic. Adevăratul creștinism nu se bazează deloc pe fapte și lucrări umane, ci numai pe harul lui Dumnezeu.Religiile false ne învață că trebuie să lucrăm pentru salvare, dar creștinismul adevărat ne învață că Dumnezeu a făcut totul în Cristos.Aceasta este o modalitate de a identifica falsurile în învățături. Minciunile lui Satan se referă întotdeauna la același lucru: spiritualitatea realizată prin efort uman și nu bazată doar pe Cristos. Apocalipsa 3:1–5 (Cartea vieții)Apocalipsa 3:1–5 (NTR)1 Îngerului bisericii din Sardes scrie-i: «Acestea sunt cuvintele pe care le spune Cel Ce are cele șapte duhuri ale lui Dumnezeu și cele șapte stele: știu faptele tale. Ai reputația că trăiești, dar ești mort.2 Trezește-te și consolidează lucrurile rămase, care sunt pe moarte, căci n-am găsit faptele tale desăvârșite înaintea Dumnezeului Meu.3 Adu-ți aminte, deci, ce ai primit și auzit! Păzește-le și pocăiește-te! Dacă însă nu te trezești, voi veni ca un hoț și nicidecum nu vei ști la ce oră voi veni la tine.4 Ai totuși în Sardes câteva nume care nu și-au pătat hainele. Ei vor umbla cu Mine, îmbrăcați în alb, pentru că sunt demni de lucrul acesta.5 Cel ce învinge va fi îmbrăcat în haine albe și nu-i voi șterge nicidecum numele din cartea vieții, iar Eu îi voi mărturisi numele înaintea Tatălui Meu și înaintea îngerilor Lui.Aceste versete par să se concentreze asupra faptelor bune, pe ideea de a fi vigilenți, de a nu ne păta hainele și de a fi victorioși. Versetul 5 spune în mod special că numai cei ce vor birui vor fi îmbrăcați în haine albe, numele lor nu va fi șters din cartea vieții sau din cartea celor mântuiți, iar Isus le va mărturisi numele înaintea Tatălui Său și înaintea îngerilor Săi. Una dintre interpretările cele mai des întâlnite ale acestui verset în lumea creștină este că unii oameni născuți din nou nu vor fi suficient de veghetori, nu vor învinge și, în cele din urmă, numele lor vor fi șterse din cartea vieții, chiar dacă au fost odată mântuiți în mod autentic. La prima vedere, aceasta pare o concluzie plauzibilă. Însă, haideți să aruncăm o privire mai atentă la fiecare verset.Aceste cuvinte erau adresate pastorului bisericii din Sardes, care reprezenta, de fapt, întreaga biserică din acel oraș. Ea era formată din două feluri de oameni: (1) mântuiți cu adevărat, (2) și cei care se numeau creștini și făceau tot felul de lucrări bune, morale, dar nu aveau o relație cu Isus Cristos și nu fuseseră niciodată născuți din nou spiritual.În versetul 1, Isus spune acestei biserici din Sardes că are niște fapte și o reputație că este în viață, dar este moartă. Ce este o biserică moartă? Este o comunitate creștină în care majoritatea oamenilor (dar nu toți) se afișează că fiind creștini buni, dar în realitate au o credință moartă. Biserica din Sardes era formată în principal din astfel de oameni. Ei făceau o mulțime de fapte și activități bune pentru comunitatea lor și probabil de aceea biserica din Sardes avea o reputație atât de bună, dar toate acele lucruri pe care le făceau erau fapte moarte pentru că nu veneau din credința în Cristos și erau doar niște fapte bune.  Versetul 2 menționează că lucrările lor nu erau perfecte (sau desăvârșite) înaintea lui Dumnezeu, întărind ideea că acești oameni nu fuseseră născuți din nou. Galateni 5:6 spune că singurul lucru care contează în Cristos este credința care lucrează prin dragoste. Pentru ca orice faptă să fie vie, ea trebuie să fie realizată dintr-o relație bazată pe credință în Cristos prin dragoste. Mai mult, Coloseni 2:9 spune că oricine este în Cristos este deja complet în El. Doar cineva în Cristos este complet și desăvârșit și, prin urmare, poate înfăptui lucrări perfecte înaintea lui Dumnezeu.S-ar putea să fi existat o perioadă în care biserica din Sardes să fi fost pe deplin vie, ceea ce înseamnă că majoritatea oamenilor din ea erau născuți din nou și eficienți în Împărăție. Însă, cu timpul, datorită unei învățături care a fost poate prea inclusivă și prea influențată negativ de cultura societății, biserica a murit. Aceasta nu înseamnă că oamenii care erau născuți din nou și-au pierdut mântuirea, ci înseamnă că biserica pe ansamblu a murit în sensul că unii credincioși autentici au plecat de acolo, s-au adăugat oameni noi și, în timp, cei morți spiritual i-au depășit numeric pe cei vii spiritual. Versetul 4 subliniază că erau, chiar și în acea biserică moartă din Sardes, câțiva oameni care încă nu-și compromiseseră credința și relația cu Cristos făcând lucrări din neprihănire de sine. Aceasta arată că erau vrednici. Nimeni nu poate fi vreodată îndreptățit prin fapte, chiar și dacă acele fapte sunt făcute prin credință. Singurul lucru care îi face pe oameni să fie demni înaintea lui Dumnezeu este neprihănirea lui Cristos și credința în acea neprihănire. Deci, acești oameni și-au păstrat convingerea puternică și credința lor simplă în neprihănirea lui Cristos. Ei nu au diluat și nici nu au murdărit această convingere amestecând-o cu eforturi umane.În versetul 2, Isus încurajează biserica să fie vigilentă și să întărească lucrurile rămase care sunt gata să moară. Ce înseamnă să fii atent sau veghetor? Să presupunem că a fi vigilent se referă la faptele bune pe care oamenii născuți din nou le fac pentru a-și menține mântuirea. Aceasta înseamnă că oamenii din acea biserică trebuiau să vegheze asupra lor înșiși și asupra acțiunilor lor, pentru a se asigura că sunt cât mai sfinți posibil încât să biruiască și să rămână mântuiți. Această presupunere creează câteva probleme semnificative. În primul rând, adăugăm lucrările lor imperfecte la credința în Cristos ca o condiție a menținerii mântuirii. Standardul lui Dumnezeu este sfințenie perfectă, pe care niciun om nu o poate atinge nici măcar după mântuire. Numai Isus a reușit aceasta. În al doilea rând, ei nu puteau ști niciodată dacă mai erau încă mântuiți sau nu. Ei s-ar fi întrebat mereu: „Suntem suficient de veghetori sau trebuie să fim mai atenți? Suntem peste pragul mediu „necunoscut” al vegherii pe care îl are Dumnezeu, dacă există așa ceva?” Nu puteau ști. Așa că „a fi veghetoare ca biserică” nu se poate referi la oamenii născuți din nou și la faptele bune ca o condiție a mântuirii.Versetele 2 și 3 dezvoltă ceea ce înseamnă a fi vigilentă ca biserică. În primul rând, întărește lucrurile care rămân, care sunt pe cale să moară. Ce sunt aceste lucruri? Ele sunt legate de învățătura curată despre credința în Cristos, dreptatea și pocăința, astfel încât oamenii să poată fi mai întâi născuți din nou și să devină vii spiritual. În al doilea rând, amintiți-vă cum ați primit și auzit mesajul mântuirii, apoi țineți strâns de acesta și pocăiți-vă ca biserică, nu ca individ. Scriitorul nu se referă la ceea ce ați primit și auzit, ci la modul în care ați primit și auzit mesajul mântuirii – adică numai prin credință și prin mărturisirea cu gura. Știu că în Noua Traducere Românească (NTR) din care am citit pasajul, versetul 3 spune: „Adu-ți aminte, deci, ce ai primit și auzit!” Însă, în traducerea Cornilescu și Biblia Traducere Fidelă 2015 (BTF2015), versetul 3 spune: „Adu-ți aminte, deci, cum ai primit și auzit.” De asemenea, și traducerea New King James Version (NKJV) din engleză la fel a translat versetul 3: cum ai primit și auzit și nu ce ai primit și auzit. În al treilea rând, o altă dovadă că audiența era formată în principal din oameni nemântuiți poate fi găsită în ultima parte a versetului 3, care spune următoarele: „Dacă însă nu te trezești, voi veni ca un hoț și nicidecum nu vei ști la ce oră voi veni la tine”. Însă, 1 Tesaloniceni 5:4-5 spune că ziua Domnului nu va prinde ca un hoț pe cei care sunt în Cristos, pentru că ei nu sunt în întuneric, ci sunt fii ai luminii:1 Tesaloniceni 5:4–5 (NTR)4 Însă voi, fraților, nu sunteți în întuneric, așa încât ziua aceea să vă apuce ca un hoț.5 Căci voi toți sunteți fii ai luminii și fii ai zilei. Noi nu suntem ai nopții, nici ai întunericului.Acest pasaj clarifică faptul că pentru oameni, a veghea sau a fi atenți, însemna ca ei să vină în Cristos și să se asigure că sunt în Cristos. În acest fel, a doua venire a lui Isus nu i-ar lua prin surprindere ca un hoț în noapte.Versetul 5 din pasajul nostru inițial (Apocalipsa 3:1–5) spune că cel ce va birui nu va avea numele său șters din cartea vieții. Să biruiască ce anume? Tentațiile de a-L părăsi pe Dumnezeu și de a renunța la mântuire din cauza numeroaselor probleme și încercări din lume care le-ar putea apărea în cale? Nu, desigur că nu, ci mai degrabă să învingă păcatul, pe diavolul, moartea și lumea. Cine sunt biruitorii în Biblie? Cine a biruit deja toate aceste lucruri? Acei oameni care în primul rând au venit în Cristos și au devenit credincioși născuți din nou. Fără aceasta, nu se poate învinge nimic, nimeni nu poate nici măcar să încerce să învingă ceva. 1 Ioan 5:4–5 spune următoarele:1 Ioan 5:4–5 (VDCL)4 Pentru că orice este născut din Dumnezeu biruiește lumea; și aceasta este biruința care a biruit lumea: credința noastră.5 Cine este cel ce biruiește lumea, dacă nu cel ce crede că Isus este Fiul lui Dumnezeu?Conform acestui pasaj, este cert că cei născuți din Dumnezeu biruiesc lumea, nu există nicio îndoială în această privință. Credința în Cristos este cea care asigură această biruință, iar acești oameni sunt cei ale căror nume nu vor fi șterse din cartea vieții. Să mai vedem câteva pasaje despre a fi victorioși.1 Ioan 2:13 (BTF2015)13 Vă scriu, taților, pentru că ați cunoscut pe Cel care este de la început. Vă scriu, tinerilor, pentru că l-ați învins pe cel rău. Vă scriu, copilașilor, pentru că L-ați cunoscut pe Tatăl.În acest verset, verbul „a învinge” este la timpul trecut, adică acei tineri l-au biruit deja pe cel rău, doar fiind în Cristos. Mai mult, acest lucru este dovedit de Romani 8:37:Romani 8:37 (NTR)37 Însă, în toate aceste lucruri, suntem mai mult decât învingători prin Cel Care ne-a iubit.Creștinii sunt mai mult decât biruitori prin Cel care i-a iubit. Ei nu înving, ci ei au învins deja în Cristos pentru că El a înfrânt lumea. Deci, a învinge înseamnă a veni în Cristos și nu a încerca să-și păstreze mântuirea până la capăt prin fapte bune. În lumina a tot ceea ce s-a spus până acum, Apocalipsa 3:5 poate fi înțeles în felul următor: „Cei care sunt născuți din nou din Dumnezeu și cred în El sunt cei care biruiesc și care nu vor fi niciodată șterși din cartea vieții”. Este o promisiune și o binecuvântare, nu o amenințare.Acum, din moment ce suntem la subiectul cărții vieții, să încercăm să aruncăm puțin mai multă lumină asupra ei și asupra cui și când este înregistrat acolo. Majoritatea creștinilor cred că Dumnezeu are un așa-numit registru numit cartea vieții în care El adaugă oameni pe măsură ce sunt mântuiți de-a lungul istoriei omenirii sau îi șterge atunci când își pierd mântuirea. Numai cei care rămân înscriși acolo vor moșteni noul cer și noul pământ. Să vedem ce are de spus Biblia despre aceasta și dacă aceste presupuneri sunt valabile.În primul rând, conform cu Apocalipsa 20:15, 21:27 și Filipeni 4:3, este adevărat că Dumnezeu are o Carte a Vieții, iar credincioșii născuți din nou sunt cu siguranță scriși în acea carte, numită și cartea vieții Mielului. De asemenea, este adevărat că numai oamenii mântuiți vor rămâne înregistrați acolo până în ziua judecății. Să citim aceste pasaje:Apocalipsa 20:15 (NTR)15 Oricine n-a fost găsit scris în cartea vieții a fost aruncat în lacul de foc.Apocalipsa 21:27 (NTR)27 Nimic necurat nu va intra în ea și nimeni care trăiește în spurcăciune și minciună, ci doar cei care sunt scriși în cartea vieții Mielului.Filipeni 4:3 (NTR)3 Iar pe tine, adevărat partener de jug, te rog, ajută-le pe aceste femei! Ele au lucrat din greu pentru Evanghelie împreună cu mine, cu Clement și cu ceilalți confrați ai mei, ale căror nume sunt în cartea vieții.În al doilea rând, conform Apocalipsei 13:8 și 17:8, se pare că există o anumită categorie de oameni care nu au fost incluși deloc în cartea vieții de dinainte de întemeierea lumii:Apocalipsa 13:8 (NTR)8 Toți cei ce locuiesc pe pământ i se vor închina, fiecare om al cărui nume n-a fost scris, de la întemeierea lumii, în cartea vieții Mielului Care a fost înjunghiat.Apocalipsa 17:8 (NTR)8 Fiara pe care ai văzut-o era și nu mai este, dar ea urmează să se ridice din Adânc și va merge spre distrugere. Locuitorii pământului, cei ale căror nume n-au fost scrise în cartea vieții de la întemeierea lumii, vor rămâne uimiți văzând fiara, pentru că ea era, nu mai este, dar va fi prezentă.În al treilea rând, Biblia nu menționează nicăieri că oamenii, de-a lungul istoriei, au fost adăugați, sau sunt adăugați, în cartea vieții în momentul mântuirii lor. Pe baza acestor scripturi ale Apocalipsei, putem, cu destul de multă certitudine, trage concluzia că restul oamenilor, în afara celor care s-au închinat fiarei, au fost înscriși în cartea vieții de dinainte de întemeierea lumii, indiferent dacă urmau să fie mântuiți sau nu (voi explica aceasta mai târziu).În al patrulea rând, în Luca 10:20, Isus le spune celor șaptezeci de ucenici, care se bucurau că demonii le sunt supuși, mai degrabă să se bucure că numele lor sunt scrise în ceruri.Luca 10:20 (NTR)20 Totuși, nu vă bucurați că duhurile vă sunt supuse, ci bucurați-vă că numele voastre sunt scrise în Ceruri!Putem presupune din nou cu destulă siguranță că Isus vorbea aici despre cartea vieții. Altfel, nu ar exista niciun motiv de bucurie dacă ar fi doar consemnați în cartea generală a celor vii sau în cărțile pentru judecată. În acel moment al istoriei, niciunul dintre ucenici nu era încă mântuit pentru că Cristos nu murise încă pe cruce. Cu toate acestea, se pare că ei erau deja înregistrați în cartea vieții. Pentru a complica și mai mult lucrurile, Iuda Iscarioteanul era printre acei ucenici și se știe clar că el a sfârșit rău și nu a fost mântuit, deși fusese consemnat în acea carte. El a fost fiul pierzării:Ioan 17:12 (NTR)12 Când eram cu ei, îi păzeam Eu în Numele Tău, pe care Mi L-ai dat. I-am păzit și niciunul dintre ei n-a pierit, în afară de fiul pierzării, ca să se împlinească Scriptura.Apoi avem oameni în Vechiul Testament, precum Avraam, regele David, Daniel și așa mai departe, care au murit fizic înainte ca Cristos să moară pe cruce și, totuși, Biblia dezvăluie că sunt mântuiți cu siguranță și astfel trebuie să fi fost scriși în cartea vieții. Dacă facem un rezumat: (1) unii oameni au fost înregistrați în cartea vieții înainte de a fi mântuiți (de exemplu, ucenicii lui Isus); (2) alți oameni au fost înscriși în cartea vieții însă nu au fost mântuiți în cele din urmă, deși au avut ocazia să facă acest lucru, și știm despre ei că sunt pierduți pentru totdeauna (de exemplu, Iuda Iscarioteanul); (3) iar alți oameni nu au avut ocazia să fie mântuiți în timpul vieții lor, dar ei sunt mântuiți pentru totdeauna și sunt înscriși în cartea vieții (părinții și profeții din Vechiul Testament).Acum, dacă încercăm să punem împreună toate aceste date, o posibilă interpretare care le-ar lega pe toate în mod logic și consecvent, fără a contrazice niciuna dintre ele, și care ar da sens tuturor acestor versete în contextul siguranței mântuirii, este următoarea:1. Dumnezeu fie a știut dinainte în mod clar, fie a hotărât în ​​mod specific (pentru scopurile Sale) că unii oameni nu vor fi mântuiți niciodată. Așa că El nu i-a inclus în cartea vieții dinainte de întemeierea lumii. Aceștia sunt închinătorii fiarei de la sfârșitul timpurilor.2.Restul oamenilor din toată istoria omenirii care urmau să fie mântuiți SAU NU, El i-a inclus oricum pe toți în cartea vieții dinainte de întemeierea lumii. Această ipoteză este susținută de 1 Timotei 2:3–4, unde Dumnezeu spune că El dorește ca toți oamenii să fie mântuiți, deși nu toți vor fi mântuiți. El dă o șansă și acordă beneficiul îndoielii tuturor oamenilor:1 Timotei 2:3–4 (NTR) 3 Acest lucru este bun și bine primit de către Dumnezeu, Mântuitorul nostru, 4 Care dorește ca toți oamenii să fie mântuiți și să vină la cunoașterea adevărului.3. Apoi, începând de acolo, Dumnezeu a șters din cartea vieții pe oamenii care au murit fizic și au părăsit această lume fără să aibă vreodată o credință mântuitoare sau să manifeste vreun fel de încredere în Dumnezeu, corespunzătoare nivelului de revelație pe care l-au avut în timpul vieții lor. Ceea ce vreau să spun prin această ultimă frază este că oamenii din Vechiul Testament care au trăit înainte de răstignirea lui Cristos au avut o revelație limitată a lui Dumnezeu și a mântuirii și nu au avut posibilitatea răscumpărării. Totuși, conform revelației pe care au avut-o, ei au făcut câțiva pași de credință înspre Dumnezeu în timpul vieții lor, au intrat într-un legământ cu El și acea credință le-a fost socotită drept neprihănire. Astfel, Avraam, Isaac, Iacov, Enoh, Noe, Moise, Iosua, David, Daniel, Rahav și alții ca ei, au rămas înscriși în cartea vieții pentru că, după cruce, li s-a dat mântuirea deși erau deja morți fizic. Acum, oamenii șterși nu au fost niciodată mântuiți de la început – adică ei nu au fost mântuiți și apoi și-au pierdut mântuirea activată, ci și-au pierdut mântuirea potențială. Nu au profitat de aceasta în timpul vieții lor.Această interpretare arată dragostea și mila lui Dumnezeu din belșug față de toți oamenii, asigură că cei care L-au primit pe Cristos nu vor fi niciodată șterși din cartea vieții și explică de ce ucenicii, inclusiv Iuda Iscarioteanul, erau deja în cartea vieții înainte de a fi mântuiți oficial. Eu cred că Iuda Iscarioteanul a fost scos din cartea vieții după moartea sa fizică.

Episode 154: Heart Failure and GDMTDr. Malave explains the four main medications that are part of the guideline-directed medical therapy of heart failure with reduced ejection fraction. Dr. Arreaza added comments and questions.  Written by Maria Fernanda Malave, MD. Edits by Hector Arreaza, MD.  You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.Brief introduction: Heart failure (HF) is a common condition that affects about 23 million people in the world, and it is estimated that 50% of cases are due to heart failure with reduced ejection fraction (HFrEF). It is a major public health concern because of the high morbidity and mortality with a 5-year survival rate of 25% after hospitalization due to HFrEF.In recent years, the management of HFrEF has evolved due to increased evidence in favor of certain medications. Guideline-directed medical therapy (GDMT) is the foundation of medical therapy for these patients, and it is the result of multiple randomized controlled trials and reviews favoring four main drug classes: 1. renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors -ACEi- and angiotensin receptor blockers -ARB), 2. evidence-based β-blockers, 3. mineralocorticoid inhibitors, and 4. sodium-glucose cotransporter 2 inhibitors -SGLT-2i-. The benefit of this therapy is mostly seen when these four groups of medications are used in conjunction. During this episode, we will provide some key elements about the prescription of these medications, but this is only an overview, and you are invited to continue learning from reputable sources.Definitions: HF is defined as the impairment of the heart to meet the metabolic demands of the body. It can be caused by multiple conditions that interfere with the filling up of the heart or conditions that prevent an effective ejection of blood out of the heart. Classification of HFrEF: Based on the EF by echocardiogram, heart failure can be classified as:Heart failure with preserved ejection fraction (HFpEF) when the EF is 50% or more.Heart failure with mildly reduced ejection fraction when EF ranges between 41-49%.Heart failure with reduced ejection fraction (HFrEF) when EF is 40% or less.GDMT: Once we make the diagnosis of HF, it is key to educate our patients and re-educate them every single visit about the importance of guideline-directed medical therapy (GDMT) and lifestyle modifications, because this can change the prognosis and exacerbation rates. Many patients think that since they are feeling well after starting GDMT they can stop it, but that's going to increase exacerbations, hospitalizations, and decrease quality of life. Key points to discuss with patients.First, discuss that GDMT are disease-modifying drugs that regulate the neurohormonal system to stop the progression of the disease. We should explain to our patients that medications should be taken despite feeling well. Also, patients should be educated about regular follow-ups and medication titration. We can even instruct our patients about increasing their furosemide dose if they observe signs of overload, such as a weight increase of 2-3 kgs in 3-4 days, tight rings, socks or bracelets, also Paroxysmal nocturnal dyspnea, dyspnea on exertion, and more.  Second, lifestyle modifications such as: quit smoking and alcohol. Additionally, in general, water restriction between 1.2-1.5L daily, salt restriction (there is no official recommendation about how many grams, but in general we recommend less than 2g daily). Third, it is highly recommended to do aerobic exercise that produces mild dyspnea since this improves cardiovascular capacity and decreases hospitalization risk. Patients should be encouraged to have their annual influenza vaccine and pneumococcal vaccine according to their own immunization schedule. According to the AFP journal, in September 2022, researchers found a clinically and statistically significant reduction in all-cause mortality for patients who received an influenza vaccine right after an MI, with a number needed to treat of 50, the effectivity of the vaccine may vary by season.GDMT, groups of medications:What are the basic medications any patient with HF should be on? At least, patients should be on angiotensin receptor blockers ARBs/ACEIs and Beta-blockers. Let's keep in mind that beta-blockers should be given cautiously in cases of exacerbation, but in general low doses are safe. We also have the angiotensin receptor/neprilysin inhibitors (ARNIs), a group of medications whose representative is the combination of sacubitril/valsartan, aka Entresto®. This medication should be the target once ARBs/ACEIs are tolerated. ARBs/ACEIs/ARNIs should be discontinued in the setting of advanced CKD, with a GFR of 30 or less. This applies to other medications used in HF such as SGLT-2 and mineralocorticoid receptor antagonist (MRA, such as spironolactone/eplerenone). Remember that SGLT-2 inhibitors should be started regardless diabetes status, and BB are safe in the setting of CKD. We also have other groups that are considered safe in patients with advanced CKD such as hydralazine/isosorbide dinitrate (combined or not), which are used in African Americans whose BP and HF symptoms do not improve with maximally tolerated dose of ARBs/ACEIs + BB.Ivabradine: Let's not forget about ivabradine, which is an SA node inhibitor like BB. Patients need to meet criteria such as a maximally tolerated dose of beta-blocker, heart rate of a least 70 or more and being on normal sinus rhythm to be started on this medication. Ivabradine does not improve survival as BB do, so even though they are not contraindicated in HF exacerbation, BB are still preferred since ivabradine does not decrease mortality.Titration and follow-ups in the HF management:-ARBs/ACEIs/ARNIs should be titrated approx. Q2 weeks until the maximally tolerated dose is achieved, ARNI should be titrated up Q2-4weeks. With these medications, we should monitor BP, potassium levels and Glomerular Filtration Rate (GFR). -BB can also be titrated up Q2weeks until the maximally tolerated dose is achieved. HR, BP and signs of congestion should be observed in patients on BB. Same for hydralazine/isosorbide, with BP follow-up. -MRA, such as spironolactone/eplerenone, these meds can be added in patients who remain symptomatic despite maximally tolerated doses of “ARBs or ACEIs or ARNIs” plus Beta-blockers. For MRA, potassium level, and GFR should be monitored every 2-3 days after initiation, 7 days after titration, monthly for 3 months, and then Q3 months. To start a patient on MRA, K+ must be lower than 5.Patients with HF should be followed up at least in a 2-week interval either via telephone, telemedicine, or clinic visit to assess symptoms, vital signs, bloodwork and to perform a physical exam. Monitoring EF: After 3-6 months of the patient´s stabilization, we should reorder an echo, EKG, BNP and Basic Metabolic Panel. The ejection fraction improves in all patients after GDMT initiation and compliance, and in some patients, this improvement is very significant, so we need to reassess EF after stabilization. Comorbidities: Also, let´s keep in mind that most of the patients have associated comorbidities such as Afib, diabetes, valve disease, or anemia. These comorbidities must be addressed either by starting anticoagulation, adjusting anti-diabetes medications, starting iron, or referring to cardiology if a valve replacement is needed.When to refer to Cardiology? Some patients will qualify for device therapy (ICD) as a primary prevention for ventricular arrhythmias that can degenerate either into torsades or ventricular fibrillation. These patients must be symptomatic, at least in 3 months of maximally tolerated GDMT, and EF between 30-35%. Symptomatic

The following question refers to Section 7.3 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. The question is asked by Palisades Medical Center medicine resident & CardioNerds Academy Fellow Dr. Maryam Barkhordarian, answered first by Hopkins Bayview medicine resident & CardioNerds Academy Faculty Dr. Ty Sweeny, and then by expert faculty Dr. Gregg Fonarow. Dr. Fonarow is the Professor of Medicine and Interim Chief of UCLA's Division of Cardiology, Director of the Ahmanson-UCLA Cardiomyopathy Center, and Co-director of UCLA's Preventative Cardiology Program. The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #28 Mr. Gene D'aMeTi, a 53-year-old African American man with ischemic cardiomyopathy and heart failure with reduced ejection fraction (LVEF 30-35%), is recently admitted with acutely decompensated heart failure and acute kidney injury on chronic kidney disease stage III. His outpatient regiment includes sacubitril-valsartan 97-103mg BID, carvedilol 25mg BID, and hydralazine 50mg TID. Sacubitril-valsartan was held because of worsening renal function. Despite symptomatic improvement with diuresis, his renal function continues to decline. He is otherwise well perfused & with preservation of other end organ function.   Throughout this hospitalization, he has steadily become more hypertensive with blood pressures persisting in the 170s/90s mmHg. What would be an appropriate adjustment to his medication regimen at this time? A Resume Losartan only B Start Amlodipine C Increase current Hydralazine dose D Start Isosorbide dinitrate therapy E Both C & D Answer #28 ExplanationThe correct answer is E – both increasing the current hydralazine dose (C) and starting isosorbide dinitrate therapy (D). Although ACEI/ARB therapy (choice A) has shown a mortality and morbidity benefit in HFrEF, caution should be used in patients with renal insufficiency. In this patient with ongoing decline in renal function, RAAS-inhibiting therapies (ACEi, ARB, ARNI, MRA) should be avoided. In this case, as his RAAS-I has been stopped, it would be reasonable to increase current therapies to target doses (or nearest dose tolerated), as these demonstrated both safety and efficacy in trials (Class 1, LOE A). Considering that his high dose ARNI was stopped, it is unlikely that either hydralazine or isosorbide dinitrate alone, even at maximal doses, would be sufficient to control his blood pressure (Options C and D, respectively). Interestingly, in the original study by Massie et. Al (1977), the decision was made to combine these therapies as the result was thought to be superior to either medication alone. ISDN would provide preload reduction, while Hydralazine would decrease afterload. Consequently, we do not have data looking at the individual benefit of either medication in isolation. In self-identified African Americans with NYHA class III or IV HFrEF already on optimal GDMT, the addition of hydralazine & isosorbide dinitrate is recommended to improve symptoms and reduce mortality and morbidity (Class 1, LOE A). In this case, as the patient has evidence of progressive renal disfunction, we are limited in using traditional RAAS-I, such as ACEI, ARB, or ARNI.

The First Principles of Prescribing Antihypertensives that can get you through your GP rotations: What are they? When do you use them? How do you tell a patient about them? === Other Links === Check out our new website ⁠⁠⁠⁠⁠1pm.wiki⁠⁠⁠⁠⁠ for the ⁠⁠⁠⁠⁠Notion document⁠⁠⁠⁠⁠, free Anki flashcards, and podcast episodes. Check out our Instagram: ⁠⁠⁠⁠⁠https://www.instagram.com/firstprinciplesofmedicine/⁠⁠⁠⁠⁠ Recorded 4 April 2023 Co-hosts: Jason D'Silva & Daniel Bontempto feat. Nhien Huynh & Fan Tang. Produced by Joshua Naylor & Adian Izwan. If you have any ideas or feedback, comment on this Notion document, or shoot us an email at ⁠⁠⁠⁠⁠hello@1pm.wiki⁠⁠⁠⁠⁠ *** We're really excited to be collaborating with Becky from Becky's notes, a UK based resource, to produce infographics for our visual learners out there. Becky's notes brings together all the key topics medical students need to know in a readily available place, reviewed by specialists in the field. These visually striking notes are a refreshing change from all the boring textbooks. You can check her out on Instagram at @beckysnotes01 and get her books at ⁠⁠⁠⁠⁠https://linktr.ee/Beckysnotes⁠⁠⁠⁠⁠ === Timestamps === (00:45) The First Principles of HTN (06:03) GASSDETH (08:32) Stratifying risk (10:02) The DRUGS (11:02) ACEi (14:23) ARBs (17:10) Thiazides (17:43) CCBs (20:03) BBlockers (23:34) Summary  (23:49) Combinations (24:56) The Triple Whammy (27:20) Medication Counselling  (31:26) Four Key Takeaways  

The NP is caring for a 68 year-old man with a 20 year-history of  type 2 DM, HTN, dyslipidaemia, obesity (BMI=32 kg/m2) stage 3a CKD who is currently taking all of the following medications at optimized doses and with adherence, ACEI, thiazide diuretic, statin, and metformin. His current A1c= 8.2%. (NL=

A 55-year-old woman with recently diagnosed hypertension was started on a standard dose of or a thiazide diuretic daily 6 weeks ago. Today her blood pressure is 128/78 mm Hg and the patient is feeling well, and clinical exam fails to reveal abnormal heart sounds or hypertensive retinopathy.  The appropriate action at this time would be to?A. Consider switching her HTN medication to a calcium channel blockerB. Continue on her current medication regimen C. Add an ACEI to enhance HTN controlD. Advise patient she needs to take her HBP for at least 1 more month prior to evaluating its effectiveness---YouTube: https://www.youtube.com/watch?v=dXpwpEaXsXc&list=PLf0PFEPBXfq592b5zCthlxSNIEM-H-EtD&index=6Visit fhea.com to learn more!

The following question refers to Section 7.3.1 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.  The question is asked by Palisades Medical Center medicine resident & CardioNerds Intern Dr. Maryam Barkhordarian, answered first by MedStar Washington Hospital Center cardiology hospitalist & CardioNerds Academy Graduate Dr. Luis Calderon, and then by expert faculty Dr. Robert Mentz.  Dr. Mentz is associate professor of medicine and section chief for Heart Failure at Duke University, a clinical researcher at the Duke Clinical Research Institute, and editor-in-chief of the Journal of Cardiac Failure. Dr. Mentz is a mentor for the CardioNerds Clinical Trials Network as lead principal investigator for PARAGLIDE-HF and is a series mentor for this very 2022 heart failure Decipher the Guidelines Series. For these reasons and many more, he was awarded the Master CardioNerd Award during ACC22. Welcome Dr. Mentz!  The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #7 Ms. Valarie Sartan is a 55-year-old woman with a history of HFrEF (EF 35%) and well controlled, non-insulin dependent diabetes mellitus who presents to heart failure clinic for routine follow up. She is currently being treated with metoprolol succinate 200mg daily, lisinopril 10mg daily, empagliflozin 10mg daily, and spironolactone 50mg daily. She notes stable dyspnea with moderate exertion, making it difficult to do her yardwork. On exam she is well appearing, and blood pressure is 115/70 mmHg with normal jugular venous pulsations and trace bilateral lower extremity edema. On labs, her potassium is 4.0 mmol/L and creatinine is 0.7 mg/dL with an eGFR > 60 mL/min/1.73m2. Which of the following options would be the most appropriate next step in heart failure therapy?  A  Increase lisinopril to 40mg daily  B  Increase spironolactone to 100mg daily  C  Add sacubitril-valsartan to her regimen  D  Discontinue lisinopril and start sacubitril-valsartan in 36 hours  E  No change  Answer #7 Explanation   The correct answer is D – transitioning from an ACEi to an ARNi is the most appropriate next step in management.   The renin-angiotensin aldosterone system (RAAS) is upregulated in patients with chronic heart failure with reduced ejection fraction (HFrEF). Blockade of the RAAS system with ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), or angiotensin receptor neprilysin inhibitors (ARNi) have proven mortality benefit in these patients.   The PARADIGM-HF trial compared sacubitril-valsartan (an ARNi) with enalapril in symptomatic patients with HFrEF. Patients receiving ARNi incurred a 20% relative risk reduction in the composite primary endpoint of cardiovascular death or heart failure hospitalization. Based on these results, the 2022 heart failure guidelines recommend replacing an ACEi or ARB for an ARNi in patients with chronic symptomatic HFrEF with NYHA class II or III symptoms to further reduce morbidity and mortality (Option D). This is a class I recommendation with level of evidence of B-R and is also of high economic value. Making no changes at this time would be inappropriate (Option E).  While it would be reasonable to increase the dose of lisinopril to 40mg (Option A), this should be pursued only if ARNi therapy is not tolerated.   Mineralocorticoid receptor antagonists (MRAs) have a class I (LOE A...

The following question refers to Section 6.1 of the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. The question is asked by Keck School of Medicine USC medical student & CardioNerds Intern Hirsh Elhence, answered first by Mount Sinai Hospital cardiology fellow and CardioNerds FIT Trialist Dr. Jason Feinman, and then by expert faculty Dr. Mark Drazner. Dr. Drazner is an advanced heart failure and transplant cardiologist, Professor of Medicine, and Clinical Chief of Cardiology at UT Southwestern. He is the President of the Heart Failure Society of America. The Decipher the Guidelines: 2022 AHA / ACC / HFSA Guideline for The Management of Heart Failure series was developed by the CardioNerds and created in collaboration with the American Heart Association and the Heart Failure Society of America. It was created by 30 trainees spanning college through advanced fellowship under the leadership of CardioNerds Cofounders Dr. Amit Goyal and Dr. Dan Ambinder, with mentorship from Dr. Anu Lala, Dr. Robert Mentz, and Dr. Nancy Sweitzer. We thank Dr. Judy Bezanson and Dr. Elliott Antman for tremendous guidance. Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #2 A 67-year-old man with a past medical history of type 2 diabetes mellitus, hypertension, and active tobacco smoking presents to the emergency room with substernal chest pain for the past 5 hours. An electrocardiogram reveals ST segment elevations in the anterior precordial leads and he is transferred emergently to the catheterization laboratory. Coronary angiography reveals 100% occlusion of the proximal left anterior descending artery, and he is successfully treated with a drug eluting stent resulting in TIMI 3 coronary flow. Following his procedure, a transthoracic echocardiogram is performed which reveals a left ventricular ejection fraction of 35% with a hypokinetic anterior wall. Which of the following medications would be the best choice to prevent the incidence of heart failure and reduce mortality? A Lisinopril B Diltiazem C Carvedilol D Sacubitril-valsartan E Both A and C Answer #2 The correct answer is E – both lisinopril and carvedilol are appropriate to reduce the incidence of heart failure and mortality. Evidence-based beta-blockers and ACE inhibitors both have Class 1 recommendations in patients with a recent myocardial infarction and left ventricular ejection fraction ≤ 40% to reduce the incidence of heart failure and to reduce mortality. Multiple randomized controlled trials have investigated both medications in the post myocardial infarction setting and demonstrated improved ventricular remodeling as well as benefits for mortality and development of incident heart failure. At this time, there is not sufficient evidence to recommend ARNi over ACEi for patients with reduced LVEF following acute MI. The PARADISE-MI trial randomized a total of 5,661 patients with myocardial infarction complicated by a reduced LVEF, pulmonary congestion, or both to receive either sacubitril-valsartan (97-103mg twice daily) or ramipril (5mg twice daily). After a median follow up time of 22 months, there was no statistically significant difference in the primary outcome of cardiovascular death or incident heart failure. At this time, ARNi have not been included in the guidelines for this specific population. Diltiazem is a non-dihydropyridine calcium channel blocker, a family of drugs with negative inotropic effects and which may be harmful in patients with depressed LVEF (Class 3: Harm, LOE C-LD). Main Takeaway:  For patients with recent myocardial infarction and reduced left ventricular function both beta blockers and ACEi have Class 1 recommendations to reduce the incidence of heart failure and decrease mortality. Guideline Location: Section 6.1

NAMIJENJENO ISKLJUČIVO ZDRAVSTVENIM DJELATNICIMA. PRISTUPOM PODCASTU POTVRĐUJETE DA STE ZDRAVSTVENI DJELATNIK.PREDAVAČ:Prof.dr.sc. ALMA MACIĆ DŽANKOVIĆ, dr.med. specijalista interne medicinesubspecijalista kardiologSarajevo, BiHLINK NA TEČAJ Pristupom na CME aktivnost na Portalu CME.ba imate priliku da na kraju iste uradite završni test, te da dobijete akreditovani CME certifikat.Telmisartan pripada grupi antihipertenziva iz klase blokatora angiotenzin receptora (ARB). Njegove komparativne prednosti u odnosu na ostale lijekove iz ove klase su brojne, jedna od najbitnijih da ima najduži poluživot u plazmi i najveći volumen distribucije, te najmanju urinarnu ekskreciju. Karakteriše ga nastup djelovanja unutar 3 sata od primjene, te maksimum djelovanja nakon 4-8 nedjelja od početka terapije. Dakle, radi se o vrlo efikasnom antihipertenzivu.Ova edukativna aktivnost je koncipirana da istakne sve navedene, kao i ostale komparativne prednosti telmisartana, kroz 3 odlična predavanja nacionalnih eksperata za kardiologiju. Tople preporuke za sve zdrvastvene profesionalce, budući da se radi o lijeku koji je u širokoj upotrebi. U ovoj epizodi podcasta donosimo audio zapis prvog predavanja iz ovog tečaja.Aktivnost je preporučena za specijaliste i specijalizante interne medicine, kardiologije, porodične medicine, a primjerena je i za studente medicine, te magistre farmacije. Ova CME aktivnost je besplatna za registrirane članove. Registracija je također, besplatna.Ova edukativna aktivnost je akreditovana od strane Ljekarske komore Tuzlanskog kantona, Farmaceutskog fakulteta Tuzla i Komore magistara farmacije TK.----------Ukoliko želite postati partner portala CME.ba ili želite da se Vaš brand ili audio poruke pojave na našim podcastima, mollimo da se javite na email info@cme.ba. Više informacija za potencijalne partnere potražite na OVOM LINKU.Zentiva Pharma d.o.o. Our aspiration is that healthcare is a right and not a privilege

Draw the flowchart from angiotensinogen onwards

NAMIJENJENO ISKLJUČIVO ZDRAVSTVENIM DJELATNICIMA. PRISTUPOM PODCASTU POTVRĐUJETE DA STE ZDRAVSTVENI DJELATNIK.PREDAVAČ:Prof.dr.sc. ALMA MACIĆ DŽANKOVIĆ, dr.med. specijalista interne medicinesubspecijalista kardiologSarajevo, BiHLINK NA TEČAJ Pristupom na CME aktivnost na Portalu CME.ba imate priliku da na kraju iste uradite završni test, te da dobijete akreditovani CME certifikat.Telmisartan pripada grupi antihipertenziva iz klase blokatora angiotenzin receptora (ARB). Njegove komparativne preednosti u odnosu na ostale lijekove iz ove klase su brojne, jedna od najbitnijih da ima najduži poluživot u plazmi i najveći volumen distribucije, te najmanju urinarnu ekskreciju. Karakteriše ga nastup djelovanja unutar 3 sata od primjene, te maksimum djelovanja nakon 4-8 nedjelja od početka terapije. Dakle, radi se o vrlo efikasnom antihipertenzivu.Ova edukativna aktivnost je koncipirana da istakne sve navedene, kao i ostale komparativne prednosti telmisartana, kroz 3 odlična predavanja nacionalnih eksperata za kardiologiju. Tople preporuke za sve zdrvastvene profesionalce, budući da se radi o lijeku koji je u širokoj upotrebi.Aktivnost je preporučena za specijaliste i specijalizante interne medicine, kardiologije, porodične medicine, a primjerena je i za studente medicine, te magistre farmacije. Ova CME aktivnost je besplatna za registrirane članove. Registracijaje također, besplatna.Ova edukativna aktivnost je akreditovana od strane Ljekarske komore Tuzlanskog kantona, Farmaceutskog fakulteta Tuzla i Komore magistara farmacije TK.----------Ukoliko želite postati partner portala CME.ba ili želite da se Vaš brand ili audio poruke pojave na našim podcastima, mollimo da se javite na email info@cme.ba. Više informacija za potencijalne partnere potražite na OVOM LINKU.Zentiva Pharma d.o.o. Our aspiration is that healthcare is a right and not a privilege

The following question refers to Section 6.2 of the 2021 ESC CV Prevention Guidelines. The question is asked by Dr. Christian Faaborg-Andersen, answered first by Houston Methodist medicine resident Dr. Najah Khan, and then by expert faculty Dr. Jaideep Patel. Dr. Patel recently graduated from Virginia Commonwealth University cardiology fellowship and is now a preventive cardiologist at the Johns Hopkins Hospital. The CardioNerds Decipher The Guidelines Series for the 2021 ESC CV Prevention Guidelines represents a collaboration with the ACC Prevention of CVD Section, the National Lipid Association, and Preventive Cardiovascular Nurses Association. Question #18 A 60-year-old Black woman with a history of hypertension and heart failure with reduced ejection fraction (EF 40%) presents to clinic for follow-up. She is currently doing well with NYHA class II symptoms. She is taking carvedilol 25 mg BID, sacubitril/valsartan 97/103 mg BID, and spironolactone 25 mg daily, all of which have been well tolerated. In clinic, her BP is 125/80 mmHg, and her HR is 55 bpm. Routine labs are within normal limits including Cr of 1.0, K of 4.0, and HbA1c of 6.0. What is the most appropriate next step in her management? A. No change in management B. Reduce beta blocker C. Add an SGLT2 inhibitor (dapagliflozin or empagliflozin) D. Add vericiguat E. Add hydralazine/isosorbide dinitrate Answer #18 The correct answer is C – Add an SGLT2 inhibitor (dapagliflozin or empagliflozin) For patients with symptomatic HFrEF, neurohormonal antagonists (ACEi, ARB, ARNI; BB; MRA) improve survival and reduce the risk of HF hospitalization. This patient is already on these agents. The addition of an SGLT2 inhibitor on top of neurohormonal blockade reduces the risk of CV death and worsening HF in patients with symptomatic HFrEF and is the next best step for this patient (Class I, LOE A). Vericiguat may be considered in patients with symptomatic HFrEF with HF worsening despite already being on maximally tolerated neurohormonal blockade (Class IIb, LOE B), but first-line therapies should be started first. Hydralazine/Isosorbide dinitrate should be considered in self-identified Black patients or people who have EF ≤ 35% or

The following question refers to Section 6.2 of the 2021 ESC CV Prevention Guidelines. The question is asked by Dr. Christian Faaborg-Andersen, answered first by Houston Methodist medicine resident Dr. Najah Khan, and then by expert faculty Dr. Jaideep Patel. Dr. Patel recently graduated from Virginia Commonwealth University cardiology fellowship and is now a preventive cardiologist at the Johns Hopkins Hospital. The CardioNerds Decipher The Guidelines Series for the 2021 ESC CV Prevention Guidelines represents a collaboration with the ACC Prevention of CVD Section, the National Lipid Association, and Preventive Cardiovascular Nurses Association. Question #18 A 60-year-old Black woman with a history of hypertension and heart failure with reduced ejection fraction (EF 40%) presents to clinic for follow-up. She is currently doing well with NYHA class II symptoms. She is taking carvedilol 25 mg BID, sacubitril/valsartan 97/103 mg BID, and spironolactone 25 mg daily, all of which have been well tolerated. In clinic, her BP is 125/80 mmHg, and her HR is 55 bpm. Routine labs are within normal limits including Cr of 1.0, K of 4.0, and HbA1c of 6.0. What is the most appropriate next step in her management? A. No change in management B. Reduce beta blocker C. Add an SGLT2 inhibitor (dapagliflozin or empagliflozin) D. Add vericiguat E. Add hydralazine/isosorbide dinitrate Answer #18 The correct answer is C – Add an SGLT2 inhibitor (dapagliflozin or empagliflozin) For patients with symptomatic HFrEF, neurohormonal antagonists (ACEi, ARB, ARNI; BB; MRA) improve survival and reduce the risk of HF hospitalization. This patient is already on these agents. The addition of an SGLT2 inhibitor on top of neurohormonal blockade reduces the risk of CV death and worsening HF in patients with symptomatic HFrEF and is the next best step for this patient (Class I, LOE A). Vericiguat may be considered in patients with symptomatic HFrEF with HF worsening despite already being on maximally tolerated neurohormonal blockade (Class IIb, LOE B), but first-line therapies should be started first. Hydralazine/Isosorbide dinitrate should be considered in self-identified Black patients or people who have EF ≤ 35% or

Sacubitril/valsartan is considered part of the backbone of guideline-recommended therapies for the management of patients with heart failure. In 2021, sacubitril/valsartan became the preferred treatment over an ACEi or ARB in patients with heart failure with reduced ejection fraction (HFrEF) because it reduces the risk of cardiovascular death and hospitalization for heart failure in nearly all adult patients with chronic heart failure. All clinicians should be familiar with the indications, dosing, safety, and monitoring of sacubitril/valsartan.  Affordability, access, and inappropriate dose titration remain major barriers to achieving optimal outcomes. Guest Authors:  Jessica Wooster, PharmD, BCACP and Elizabeth Yett, PharmD, BCACP Special Guest:  Dustin (DJ) Clark, PharmD, BCACP Music by: Good Talk

How do you counsel patients on beta blockers? Is one beta-blocker better than the other? What is preferred: ACEi, ARBs or ARNIs? What are the pros and cons of each? How does spironolactone compare to eplerenone? When do you stop mineralocorticoid receptor antagonist? What are risks with SGLT2 inhibitors? How do you initiate GDMT? Which meds do you start first and in what order?Show notes, Transcript and References:  https://www.coreimpodcast.com/2022/05/11/5-pearls-on-guideline-directed-medical-therapy/Sponsor: https://go.amboss.com/GDMTGet CME-MOC credit with ACP: https://www.acponline.org/cme-moc/cme/internal-medicine-podcasts/core-im Time stamps:03:13 Pearl 112:14 Pearl 220:36 Pearl 326:42 Pearl 432:16 Pearl 5Tags: IM Core, CoreIM, heart failure with reduced ejection fraction, GDMT, treatment, cardiology

CardioNerds  (Amit Goyal, Daniel Ambinder) and special co-host Dr. Mark Belkin, join the Journal of Cardiac Failure Family to discuss the 2022 ACC/AHA/HFSA Guideline for The Management of Heart Failure. The JCF Editor-In-Chief Dr. Robert Mentz, Deputy Editor Dr. Anu Lala, and FIT editors -- Dr. Vanessa Bluemer, Dr. Ashish Corrhea, and Dr. Quinton Youmans -- share their hot takes and practical takeaways from the guidelines. At JCF, we're privileged to share this important document that will support improved care for those living with heart failure,” stated Editor-in Chief Dr. Robert J. Mentz and Deputy Editor Anu Lala. “The 2022 guidelines convey patient-centered updates regarding the language we use to communicate disease considerations (e.g., stages of HF) and practice-changing guidance around the diagnosis and management of HF including newer therapeutics (e.g., SGLT2i). There is an emphasis not only on managing HF but also on how to treat important comorbidities as part of the holistic care for patients living with HF." 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure Executive Summary A Clinician's Guide to the 2022 ACC/AHA/HFSA Guideline for the Management of Heart Failure by Dr. Michelle Kittleson CardioNerds Heart Success Series PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Guideline Top 10 Take-Home Messages - Guideline for The Management of Heart Failure 1. Guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction (HFrEF) now includes 4 medication classes that include sodium-glucose cotransporter-2 inhibitors (SGLT2i). 2. SGLT2i have a Class of Recommendation 2a in HF with mildly reduced ejection fraction (HFmrEF). Weaker recommendations (Class of Recommendation 2b) are made for ARNi, ACEi, ARB, MRA, and beta blockers in this population. 3. New recommendations for HFpEF are made for SGLT2i (Class of Recommendation 2a), MRAs (Class of Recommendation 2b), and ARNi (Class of Recommendation 2b). Several prior recommendations have been renewed including treatment of hypertension (Class of Recommendation 1), treatment of atrial fibrillation (Class of Recommendation 2a), use of ARBs (Class of Recommendation 2b), and avoidance of routine use of nitrates or phosphodiesterase-5 inhibitors (Class of Recommendation 3: No Benefit). 4. Improved LVEF is used to refer to those patients with previous HFrEF who now have an LVEF >40%. These patients should continue their HFrEF treatment. 5.Value statements were created for select recommendations where high-quality, cost-effectiveness studies of the intervention have been published. 6. Amyloid heart disease has new recommendations for treatment including screening for serum and urine monoclonal light chains, bone scintigraphy, genetic sequencing, tetramer stabilizer therapy, and anticoagulation. 7. Evidence supporting increased filling pressures is important for the diagnosis of HF if the LVEF is >40%. Evidence for increased filling pressures can be obtained from noninvasive (e.g., natriuretic peptide, diastolic function on imaging) or invasive testing (e.g., hemodynamic measurement). 8. Patients with advanced HF who wish to prolong survival should be referred to a team specializing in HF. A HF specialty team reviews HF management, assesses suitability for advanced HF therapies, and uses palliative care including palliative inotropes where consistent with the patient's goals of care. 9. Primary prevention is important for those at risk for HF (stage A) or pre-HF (stage B). Stages of HF were revised to emphasize the new terminologies of “at risk” for HF for stage A and pre-HF for stage B. 10.Recommendations are provided for select patients with HF and iron deficiency, anemia, hypertension, sleep disorders,

Writing Group for the CODA Collaborative. Patient factors associated with appendectomy within 30 days of initiating antibiotic treatment for appendicitis. JAMA Surg 2022 Jan 12; [e-pub]. Now, investigators have explored in a secondary analysis of  The CODA Collaborative. A randomized trial comparing antibiotics with appendectomy for appendicitis. N Engl J Med 2020 Oct 5; [e-pub]. (data from a previous randomized antibiotics-versus-surgery trial (NEJM JW Gen Med Dec 1 2020 and N Engl J Med 2020; 383:1907). Have looke at the data to see could we predict factors that make you more likely to appendectomy and fail antibiotic therapy.  They identified 735 patients who had been randomized to antibiotic treatment; 154 (21%) of these patients underwent appendectomy within 30 days. Overall, 29% of patients in the antibiotics group underwent appendectomy within 90 days (41% of those with appendicolith vs. 25% without). The authors suggest hey maybe this appendicolith is the magic answer of who will fail therapy—maybe!! BUT remember this is secondary analysis so this is only hypothesis generating even a secondary analysis of a rct is just hypothesis. You need a new RCT to actually show causation.  Also as stated in the editorialists note that in subsequent analyses of this same data set, nearly 50% of patients underwent appendectomy within 2 years, regardless of the presence of an appendicolith, so an initial nonsurgical approach might only delay surgery. Some say 50% still going to surgery is terrible but I say even if 50% prevented from having surgery that is still 50% of people are being prevented from a surgery      Acetazolamide to Prevent Adverse Altitude Effects in COPD and Healthy Adults | NEJM Evidence Trial 1 was a randomized, double-blind, parallel-design trial in which 176 patients with COPD were treated with acetazolamide capsules (375 mg/day) or placebo- COPD patients had oxygen saturation measured by pulse oximetry of 92% or greater  primary outcome in trial 1 was the incidence of the composite end point of altitude-related adverse health effects (ARAHE)== Criteria for ARAHE included acute mountain sickness (AMS) and symptoms or findings relevant to well-being and safety, such as severe hypoxemia, requiring intervention. In trial 1 of patients with COPD, 68 of 90 (76%) receiving placebo and 42 of 86 (49%) receiving acetazolamide experienced ARAHEThe number needed to treat (NNT) to prevent one case of ARAHE was 4EVEN at NNT of 4 you  have to realize that still 50% of those with COPD required intervention to go back down to lower level.   Trial 2 comprised 345 healthy lowlanders.The primary outcome in trial 2 was the incidence of acute mountain sickness AMS assessed at 3100 m by the Lake Louise questionnaire score (the scale of self-assessed symptoms ranges from 0 to 15 points, indicating absent to severe, with 3 or more points including headache, indicating acute mountain sickness AMS).In trial 2 of healthy individuals, 54 of 170 (32%) receiving placebo and 38 of 175 (22%) receiving acetazolamide experienced acute mountain sickness AMS  The NNT to prevent one case of acute mountain sickness AMS was 10 (95% CI, 5 to 141).So use the acetazolamide still 1 in 5 individuals experience acute mountain sickness    Annals for Hospitalists Inpatient Notes - Clinical Pearls—Stopping, Starting, and Optimizing Guideline-Directed Medical Therapy in Patients Hospitalized for Heart Failure With Reduced Ejection Fraction | Annals of Internal Medicine (acpjournals.org) Treat with??Foundational medical therapy for HFrEF consists of comprehensive disease-modifying quadruple medical therapy, including angiotensin receptor–neprilysin inhibitors (ARNIs), β-blockers, mineralocorticoid receptor antagonists, and sodium–glucose cotransporter-2 inhibitors (1). Quadruple medical therapy is estimated to cumulatively reduce the relative risk for death by 73% over 2 years, with a number needed to treat of 3.9 to save 1 life  compared with traditional therapy using an ACEI and a β-blocker, treating a 55-year-old patient with comprehensive disease-modifying quadruple therapy projects to increase life expectancy by more than 6 years Approximately 1 in 4 patients hospitalized for worsening HFrEF die or are rehospitalized within 30 days of discharge --- Deferring in-hospital initiation is consistently associated with medications never being initiated in the outpatient setting, or initiated after substantial delaySTART THEM IN THE HOSPITAL-- There is no evidence to suggest that “go slow,” “one medication change at a time,” or “defer to outpatient” approaches improve medication tolerance or accomplish anything beneficial  If you mix a bunch of moon pies in a trash can you get what sounds like a great time but if you mix a bunch of cow pies in a trash can you just get poop Clearly seen in this next article Vitamin D supplementation for the treatment of migraine: A meta-analysis of randomized controlled studies - ClinicalKey  meta-analysis aims to explore the efficacy of vitamin D for migraine patients. Six RCTs and 301 patients were included in the meta-analysis. On average these people were having around 7 migraines per months and compared to control the vit d group decrease headache days by about 1.5 per month compared to placebo or UC So you say vit d works for something!!Not so fast Remember I would like a 25 yr old cut my hair by not 5 five year olds…. Sadly these studies were 5 yr olds UC could be nothing. Well vit d beating nothing isn't hard, we know placebo is real Even beating placebo isn't hard when it is open label or you are not blinded to the active arm. If I say, yes you are getting this drug vit d that will help your headaches you are going to believe it much more than if I just give you a pamphlet.  The authors in the discussion state “Higher vitamin D levels is associated with lower risk of migraine “ Well ya that is true but having a higher vitamin d level is also associated with going outside more. And going outside more is associated with no having a migraine.  High vit d level is amazing!! I love it but replacing it still seems to do nothing however if you want a high level and want to go outside and get a high level then I think that is a great idea and speaking of great ideas—    Here is a sad but enlightening article— Home pregnancy test use and timing of pregnancy confirmation among people seeking health care - ClinicalKey The researchers found that 74% of survey respondents took a home pregnancy test as the first step in confirming a suspected pregnancy;  Respondents who took home pregnancy tests confirmed pregnancy 10 days earlier than those who first tested at a clinic. (duh statements- if you test at home you find out sooner, this is so obvious an a no brainer--- BUT Confirmation of pregnancy at greater than 7 weeks' gestational age was higher among adolescents, Latina versus white women, food-insecure versus -secure women, and people with unplanned pregnancies. Those that did not test at home cited concerns about test accuracy (42%) and difficulties accessing one (26%). While overall 1/5 21% confirmed pregnancy at ≥7 weeks gestation, confirmation at ≥7 weeks was higher among adolescents versus young adults (47%!! vs 13%, p = 0.001), Latina versus white women (28% vs 11%, p = 0.02), food insecure versus secure women (28% vs 17%, p = 0.06), and people with unplanned versus planned/mistimed pregnancies (25% vs 13%, p = 0.07). Latina and food insecure women discover their pregnancy at the same time or rate as individuals with unplanned pregnancy!!! one in 5 confirm pregnancy at 7 weeks gestation or later and in those Latina, poor, or unplanned It is ¼ at >7weeks this obviously effects prenatal care and Gestational bans in the first trimester will disproportionately prevent young people, people of color, and those living with food insecurity from being able to access abortion.This is tough but it is this data that reminds me and should remind us that life is not equal and healthcare is not equal and certain populations and groups do need our help more than others.

The challenge of to use or not to use ACEI/ARBs in patients with COVID-19

Trying to keep up with the medical literature, but it's another COVID Christmas and you can't wait to unwrap your stocking filled with lateral flows, rota gaps, and cancelled leave…you're ears are in the right place.Barney & Jon are back to cover the latest medical literature.We cover:How long is too long for a liver transplant?The harms of tramadol?HFPeF gets a breakthrough.ARB vs ACEi: a battle you didn't know you cared about.Personalised your steroids in COPD.Why Iron & infections don't mix?Studied so much they should call it COVIDamin DObesity trends that break the scales.For full episode details and show notes, head to journalspotting.comGet in touch @JournalSpotting on Twitter, Instagram, or Facebook.or email us journalspotting@gmail.com

In this Part 1 of our two-part series on acute heart failure, Anton is joined by Dr. Tarlan Hedayati and Dr. Bourke Tillman to answer such questions as: how does PoCUS compare with clinical assessment and CXR in diagnostic accuracy for acute heart failure? How do we best integrate PoCUS in the our assessment and management of the patient with acute heart failure? What is PPV HAVoC and how can we use it to optimize acute heart failure management goals? What should be our specific goals of management in the acute heart failure depending on the underlying cause? How does high flow nasal cannula (HFNC) compare to non-invasive positive pressure ventilation (NIPPV) in the management of acute heart failure? How should we interpret the C3PO trial in the context of the world's literature on NIPPV in acute heart failure? How should we dose nitroglycerin to maximize its effects without dumping the blood pressure in patients with SCAPE and those without SCAPE? How should we best time and dose furosemide in the acute heart failure patient with renal insufficiency? Is there any role for morphine or ACEi in the ED management of acute heart failure? What are best anxiolytic medication choices in acute heart failure? Is there any role for second line diuretics in the management of acute heart failure in the ED? and many more... The post Ep 163 Acute Heart Failure ED Management – PoCUS, Oxygenation Strategies, Medication Strategies, PPV HAVoC and SCAPE appeared first on Emergency Medicine Cases.

Join us for this rapid fire review of systems featuring our top pearls and articles LIVE! from the TriService ACP conference. Matt and Paul serve up their favorite practice changing knowledge food on antibiotics, MRSA, hair loss, dementia, seizures, diabetes, medications for hypertension, foods for constipation, diverticulitis, colon cancer screening, colon polyps, chronic sinusitis, chronic cough, treatment of uterine bleeding, and more!  No CME for this episode, but check out curbsiders.vcuhealth.org for past CME offerings! Episodes | Subscribe | Spotify | Swag! | Top Picks | Mailing List | thecurbsiders@gmail.com | Free CME! Credits Matthew Watto MD, FACP; Paul Williams MD, FACP    Cover Art: Sawyer Watto Editor: Matthew Watto MD (written materials); Clair Morgan of nodderly.com Sponsor: BetterHelp Get 10% off your first month at betterhelp.com/curb.         Sponsor: ACP's National Internal Medicine Day Help the American College of Physicians celebrate National Internal Medicine Day on October 28th. Visit https://www.acponline.org/NIMD2021 to learn how you can show your internal medicine pride. Be sure to tag @ACPInternists and use the hashtag #NationalInternalMedicineDay. CME Partner: VCU Health CE The Curbsiders are partnering with VCU Health Continuing Education to offer FREE continuing education credits for physicians and other healthcare professionals. Visit curbsiders.vcuhealth.org and search for this episode to claim credit.  Show Segments Intro, disclaimer ID: Shorter is better; MRSA swabs; Antibiotics for diverticulitis Endo: Prediabetes in older adults,  MSK: Knee OA, orthopedic surgery Derm: Alopecia Neuro: Seizures, dementia quick typing Cardio: Coffee and arrhythmias; Hypertension management, ACEi vs ARBs Respiratory: Chronic cough and sinusitis GI: CRC screening, foods for constipation GU: treatment of uterine bleeding Addiction Medicine: smoking cessation, buprenorphine Outro

Dr Dave Maplesden and Dr Jo Scott-Jones discuss "snippets" of clinical information relevant to New Zealand General Practice in this monthly conversation. This time, referring patients - the importance of using agreed processes for acute admissions and bowel screening, emaglifozin side effects, boron containing medications, hyperkalaemia, the choice of an ACEi or an ARB, and how not to prescribe Ivermectin for covid.

Before we ask a patient to take any drug we should be confident that the benefits outweigh the risks. This involves considerations like duration of therapy and whether the drug is being used to treat a disease versus prevent it. But even more important is an understanding of how the pharmacology of the drug matches up to the pathophysiology of the disease. The better we understand both, the better we'll be at deciding when to use any drug for any disease. In todays episode we apply these tenets of drug therapy to a common question, "does my patient with diabetes need to be on an ACEi or ARB?" To answer that question, we'll discuss the merits of drugs for disease prevention versus disease treatment. The use of risk factors for disease may or may not be sufficient to justify drug therapy. An LDL cholesterol of 220 is sufficient to initiate cholesterol lowering therapy. But is diabetes a sufficient reason to initiate an ACEi or ARB? We'll figure that out....and whether or not the answer surprises you, we'll learn things along the way that will be useful in virtually all settings of applied pharmacotherapy.

Macht Hochdruck Nasenbluten oder Nasenbluten Hochdruck? Dieser Frage recherchierte Jana hinterher. Der DEGAM-Entsandte bei der NVL Diabetes mellitus Til Uebel beantwortet unsere Fragen zur Überarbeitung der NVL D.m., Thomas beantwortet die Hörer*Innenfrage nach der Sinnhaftigkeit einer Kombination von ACE-Hemmern und AT-II-RA.

Back by popular demand…all two of you…the second chapter of The Clinical Physiology of Acid Base and Electrolyte Disorders. Chapter Outline- Renal Circulation and GFR - RBF is 20% of cardiac output - In terms of mL per 100 g organ weight it is 4x the liver and exercising muscle and 8x coronary blood flow! - After the glomeruli the efferent arteriole have two fates - Peritubular capillaries in the cortex - Peritubular capillaries are not necessarily associated with their parent glomeruli. Weird. - Vasa recta from juxtamedullary glomeruli in the medullaJoel Says: This seems wrong. Solute balance can be maintained down to a very low GFR. The R^2 here would be very low. Prove me wrong. - States that GFR is an important determinant of solute and water excretion. - Glomerular anatomy and function - Structure Four editions of the Bud Bible up top and a copy of Bud Light on the bottom. - Glomerulus is a tuft of capillaries - Enclosed in a capsule of epithelial cells, called Bowman's capsule - The epithelial cells of Bowman's capsule are continuous with the epithelial cells of the proximal tubule Looking at scanning EMs of the glomerulus is one of life's simple pleasures—Josh. Josh says: Look at the review in Nature Reviews Nephrology from Rachel Lennon's groupComplexities of the glomerular basement membrane - Filtration barrier - Epithelial cell (podocyte) - Epithelial cells adhere to the basement membrane via foot processes and the foot processes have slit diaphragms - Basement membrane New Super-resolution structure of the GBM: https://elifesciences.org/articles/01149 Hi res microscopy is really hi-res. Technique is call ed STORM. Melanie talks about conduits through the glomeruli. Here is a cool review: Why until just now? Undiscovered uniqueness of the human glomerulus! by L. Gabriel Navar, Owen RichfieldAm J Physiol Renal Physiol. 2018 Nov 1; 315(5): F1345–F1346. Published online 2018 Aug 15. doi: 10.1152/ajprenal.00369.2018 PMCID: PMC6293291 - Produced by both the endothelial cells and podocytes - Formed from type IV collagen - Abnormalities of type 4 collagen cause Alport - The gene coding for the alpha 5 chain is the culprit - COL4A5 - Abnormal Alpha 3 and 4 chains can also cause hereditary nephritis - Has other substances - Laminin - Nidogen - Heparin sulfate proteoglycans - Provides the negative charge - Enthothelial cell (fenestrated) - Protein excretion - Glomerular function: allow filtration of small solutes (Na and urea) while preventing filtration of larger molecules - Insulin MW 5,200 is freely filtered (upper range of freely filtered) - Preventing loss of protein prevents - Negative nitrogen balance - Development of hypoalbuminemia - Infection from loss of immunoglobulin - Size and charge selectivity of the GBM - pores are between cords of type 4 collagen - The epithelial cells and slit diaphragms matter - Macromolecules that pass through GBM can accumulate underneath the epithelial layer - Isolated GBM in invitro studies is much more permeable to than intact glomerulus - There is increased protein filtration in areas where the epithelial cells have detached from the GBM Josh really likes this figure from another Nature Reviews Nephrology paper. This one by Moeller and Chia-Gil. - Mutations in nephrin, localized to the slit diaphragm causes congenital nephrotic syndrome - Charge selectivity is important - Neutral and cationic particle are more likely to be filtered - Albumin (negative charge) is filtered 5% as well as same size neutral dextrans - In glomerular disease, while there is increased filtration of proteins there is decreased filtration of small solutes due to loss of glomerular surface areaJC says: Take a look at this research on the serving coefficient in glomerular disease. Some surprising results.Glomerular dysfunction in nephrotic humans with minimal changes or focal glomerulosclerosis - Why do people in remission have what appears to be spilling more high molecular radius particles than normal and why do patients with active MCD have lower clearance across all molecular diameters? - Other glomerular functionsJosh says: Take a look at this interesting paper by Butt et alA molecular mechanism explaining albuminuria in kidney disease - Synthetic - Epithelial cells produce GBM - Phagocytic - Remove circulating macromolecules that pass through GBM and get trapped in subepithelial spaceJosh says: The sFLT1 (soluble VEGF receptor) relationship to preeclampsia is just so cool. And here's the paper:Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsiaAnd in the NEJM: VEGF Inhibition and Renal Thrombotic Microangiopathy - Endocrine - Enthothelial cells regulate vascular tone by releasing - Prostacyclin - Endothelin - Nitric oxideJC says: Do yourself a favor and spend some time learning about extraglomerular mesangial cells with Stuart Shankland Extraglomerular origin of the mesangial cell after injury. A new role of the juxtaglomerular apparatusJoel adds, if you ever get a chance to party with Dr. Shankland, don't skip out. - Mesangial cells, two types - Intrinsic Mesangial cell - Microfilaments similar to smooth muscle - Responds to Ang2 - Regulates glomerular hemodynamics - Can release cytokines - Can respond to cytokines by proliferation - Circulating macrophages and monocytes - Phagocytic function - Clear molecules that get through the endothelial wall but cant get through the GBMJosh says, “Topf, get it right. Its Ree-nin not renin. Classic letter to JAMA. - Renin-Angiotensin System - Afferent arteriole contain specialized cells called juxtaglomerular cells - Produce prorenin which cleaved into renin - Stimuli for renin release - Hypotension - Volume depletion - Increased sympathetic activity - Renin catalyze the production of ang1 from angiotensinogen - Ang1 is catalyze to Ang2 by ACE located in the - Lung - Endothelial cells - Glomeruli itself pic.twitter.com/DaDfS7u8se— Roger Rodby (@NephRodby) February 22, 2021 - Discussion of local renin and Aniotensinogen - Explains why ACEi are useful even with low systemic renin levels and Ang2 - Actions of Ang2 - Sodium and water retention - By direct Na reabsorption in the early PT (and in the proximal tubule, water is permeable to the epithelium so every sodium reabsobed, brings a water molecule along for the osmotic ride. - Stimulates the Na-H antiporter - 40-50% of Na reabsorption in the S1 segment of the PT is due to Ang2 - By stimulation of aldosterone - Ang2 that stimulates Aldo comes from the kidney and from the adrenal gland itself - VasoconstrictionJosh talks angiotensin:Tenses the angios--love this Melanie!1961 paper from del Greco (who's endowed chair Dan Batlle has now) trying AT2 in "hopeless" patients and dialysis patients:https://jamanetwork.com/journals/jama/article-abstract/332265Great EM-crit/pulmcrit discussion here:https://emcrit.org/emcrit/deeper-vasopressors-athos-3/and caveats here:https://emcrit.org/pulmcrit/angiotensin-ii/ - Arteriolar vasoconstriction - Ang2 important for raising BP in RAS - Ang2 important in maintaining BP with volume depletion or in CHF, liver disease - Giving ACEi to cirrhosis can cause BP to dump 25 points - Regulation of GFR - Affects constriction at afferent arteriole and efferent arteriole - Mediated via thromboxane JC talks about the ATHOS trial and how there is a signal for improved outcomes especially in patients requiring renal replacement therapy.Angiotensin II for the Treatment of Vasodilatory ShockOutcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II - Afferent arteriole starts bigger so reductions have less of an effect than constriction does on the narrower efferent arteriole. - This results in a fall of RBF due to increased resistance but maintaining GFR by increasing inrtaglomerular pressure. - Also stimulates prostaglandins which are vasodilator, modulating this affectJoel says: You haven't heard of the Trolly Problem? Oh you need to take 5 minutes and read this. - It can stimulate contraction of the mesangium reducing surface area of the glom reducing filtration. - It sensitizes the afferent arteriole to TG feedback so it can reduce glomerular flow in response to increased chloride detection in the TLoH. - Control of renin secretionEver wanted to know about intrarenal renin concentrations? Yeah, me neither. But JC's got you covered: Endogenous angiotensin concentrations in specific intrarenal fluid compartments of the rat. - Primarily sodium intake, increased intake results in less renin - Mediated by baroreceptors - Baroreceptors in afferent vessel wall - Cardiac and arterial baroreceptors which activate the sympathetic nervous system and catecholamines which then stimulates reninRoger says: Do your self a favor and read about Yanomamo IndiansBlood pressure and electrolyte excretion in the Yanomamo Indians, an isolated population - Cells of the macula densa in the early distal tubule which detect decreased chloride delivery - This allows loop diuretics to be particularly effective at increasing renin as they block chloride resorption - Suppression of renin in response to chloride is mediated by adenosine - Stimulation of renin in response to decreased chloride is mediated by PGE - The PGE cause local vasodilation so the kidney maintained a rich blood flow while using renin and Ang2 to cause systemic vasoconstrictionAnna's notes for the deep dive in glomerular barrierOur understanding is based on technology available at the time. Even in 1920s, there was thought that tubular reuptake of protein may be important, but studies never demonstrated this til 2007 and even then are debated. 2007 Russo, et al (and BM at IU!) showed that The normal kidney filters nephrotic levels of albumin and that failure of retrieval by proximal tubule cells is what separates proteinuria from nonproteinuria. This was countered by a study in 2009 demonstrating much lower GSC and suggesting that the high GSC in the 2007 could be the result of nonphysiologic states.Check out this 2008 debate in JASN regarding the validity of the charge model and “normal” albumin in the glomerular filtrate. Hotly debated with too many studies to cite. 2017: Lawrence et al publish their findings that the GBM and podocyte processes are sufficient and the slit diaphragm likely does not exist. They used labeled proteins and confocal microscopy to determine migration of particles through the enodthelium and GBM. They also injected NaSCN oligoclusters from the size of albumin (66kDa)up to the size of IgG dimers (300 kDa) into mice, then fixed. The size-sensitive permeation into the lamina densa of the GBM and the podocyte glycocalyx of albumin and uptake of any “escaping” albumin by the proximal tubule was also observed. This countered the common prior conception that the slit diaphragms pores are the site of albumin “capture.” For your reading pleasure the review of Clinical Physiology of Acid-Base and Electrolyte Disorders Fourth Edition in Annals of Internal Medicine

Today we have a special guest, Dr. Jared Bunch, an international expert in atrial fibrillation and ablation, to talk about the state of atrial fibrillation and which patients benefit from early catheter ablation based on two new trials published last week in the NEJM. We also talk about whether you should stop ACEi or ARBs in patients admitted with COVID-19, whether oral antibiotics are adequate for uncomplicated appendicitis, and whether you should target a high (90 mmHg) or low (60 mmHg) paO2 in patients with respiratory failure. STOP-AF First trialEARLY-AF trialACEi and ARBs in COVID-19IV vs Oral Antibiotics for AppendicitisRifaximin after TIPS to Prevent HEReimagining Endocarditis Care in an Opioid EpidemicLower vs Higher Oxygen TargetsMusic from https://filmmusic.io"Sneaky Snitch" by Kevin MacLeod (https://incompetech.com)License: CC BY (http://creativecommons.org/licenses/by/4.0/)

Autoimmune mothers likely don't actually have more ADHD kids. If you patient is in the hospital we now have a RCT to answer the question about ACEI starting or stopping. Finally, there are problems around COVID we don't even know about and it has nothing to do with contracting COVID19. Association of Maternal Autoimmune Disease With Attention-Deficit/Hyperactivity Disorder in Children | Attention Deficit/Hyperactivity Disorders | JAMA Pediatrics | JAMA Network Doesn't say what the authors think that it says – or perhaps it does and that is the problem with most studies in pregnancy…. The authors conclusions were “In this cohort study, maternal autoimmune diseases were associated with increased ADHD among children.” Wiat autoimmune disorders in mom and boom big time risk of ADHD in children! Better brain has true celiac so this is something I am interested—it sparked my attention! population-based cohort analysis of 831,718 infants and mothers in the end the researchers matched almost 13,000 children whose mother's had an autoimmune disease with approximately 50,000 children whose mothers did not have an autoimmune disease and when they crunch through all of the numbers those individuals whose mothers did not have an autoimmune disease were diagnosed with ADHD 5.48 cases per 1000 boys and 1.70 per 1000 girls BUT if your mom had an autoimmine disease then your risk of ADHD SHOT UP. From 5.5 for boys to 6.9 and from 1.7 for girls to 2.3. Yes that’s right an extra case of ADHD for every 700boys and an extra case of ADHD for every 2000 girls--- multiple things about the study- first of all not very impressed by the findings. Ousley is a cohort study so they're just looking at groups of patient's at different points of time. However may be the mothers who have autoimmune disorders are more likely to go to the doctor for their illness and thus more likely to take the child to the doctor. Or mothers who have autoimmune disorders are probably more likely to have health insurance for their medical condition and thus more likely once again to take their children to the doctor. After all he can be diagnosed with ADHD or any other illness unless you go to the doctor to get the diagnosis. Next this is a perfectly example of absolute and relative risk reduction which is often miss under still by many medical students, resident's, and even attending physicians. Left look at the event rate of ADHD in girls. It was 1.7 per thousand for those individuals who did not have a mother with an autoimmune disorder and the event rate went up to 2.3 cases of ADHD per thousand for those girls whose mother has an autoimmune disorder. The difference between 1.7 and 2.3 is 0.5. Thus you could say that if you have a mother with an autoimmune disease then there is a 0.5 per thousand increase rate of ADHD. Or since 0.5 is about a third or 33% of of 1.7- I could potentially say that having a mother with an autoimmune disorder increases your risk of ADHD as a female child by 33%. In both statements I'm saying the same thing-------------- rant A reminder- The authors conclusions were “In this cohort study, maternal autoimmune diseases were associated with increased ADHD among children.” So maybe this article does say what the authors think that it said but unless you read the article you might be tricked into thinking that this was a substantial finding and worth long debates and discussion about. One of many problems with pregnancy litature is the small almost insignificant findings. you see there actually was an increase but that increase was so small---- the reason being is that most pregnancies go off without a hitch. Most pregnancies don't have any complications. Most pregnancies that are carried to term delivery are absolutely fine so when you find even a small increase in the numbers you can report regardless if it worth your time to know about or think about. The next article is the ultimate questiongin medicine article Effect of Discontinuing vs Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on Days Alive and Out of the Hospital in Patients Admitted With COVID-19: A Randomized Clinical Trial | Critical Care Medicine | JAMA | JAMA Network Remember at the beginning of covid I did a podcast and I talked about ACE and ARBs and said I am still writing for them. This belief the are bad comes from bad evidence Actually not even evidence—just opinion pieces such as a piece in journal of htn back in may titled- Like Can angiotensin receptor-blocking drugs perhaps be harmful i... : Journal of Hypertension (lww.com) Can angiotensin receptor-blocking drugs perhaps be harmful in the COVID-19 pandemic? Some of us stopped acei on everyone. You make a fancy little drawing and explaination of a possible mechanism and many people fall victim and believe you. This is why drug reps are so successful. For majority of physicians they don't actually have the prove any benefit or outcome just a bunch of drawings with fancy words and potential mechanisms of how it could work. Others of us demand hard outcomes and appropriate clinical trials Well now we have our results in this JAMA article which is the first randomized control trial of roughly 650 patient's hospitalized with mild to moderate COVID-19 who were taking either an ACE inhibitor or an angiotensin II receptor blockers (ARBs) on admission. Patient's were then randomized to either discontinue the ACE inhibitor or angiotensin II receptor blocker or to continue it. The primary outcome was the number of days alive and out of the hospital after 30 days. The secondary outcomes included death, cardiovascular death, and COVID-19 progression And there was absolutely no difference no matter what you looked at Continue the ACE OR ARB when you patient is admitted to the hospital with mild to moderate covid19 And the last article should make you think Make you think Progression of Myopia in School-Aged Children After COVID-19 Home Confinement | Global Health | JAMA Ophthalmology | JAMA Network There are problems with covid 19 we cant even see yet. They have nothing to do with getting covid. They have to do with not getting covid. The social isolation is one of them but another one is the concern is whether home confinement 4 children may have a burden on their eyes. Less time outside = less time playing and more time inside likely in front of some sort of screen whether it be a computer screen or a TV screen or a tablet screening. So in the study the authors set out to fine if the prevalence of myopia in school children during Covid 19 was affected. The theory being that children are spending more time in front of a screen and less time outside and thus the eyes are not encouraged to grow any look for anything greater than something that is 2 feet in front of the face. This study was paced out of China however I think that the results of likely applicable to everyone. Photoscreenings have been performed annually on children in 10 elementary schools since 2015- this is usually over 100,000 children participating each year. In each ear the authors calculated an estimated prevalence of myopia And in 2020 the rates of myopia s/p covid quartine the changes were scary. For 8yr olds the prevalence in previous years was 27% and it jumped up to 37%. For seven year olds the prevalence was 16% and jumped up to 26% and for 6 year olds the prevelance of myopia was 5.7% and relatively speaking it jumped up 400% or and absolute of 21% This substantial myopic shift was not seen in any other year-to-year comparison, What does this mean?? Sure there is a change but what does it mean?? And the answer is we don’t totally know and we wont know We do know currently that 1 in 3 people with high myopia becomes severely visually impaired, mostly at working age. So the potential health problem is very bad. This is not me saying we shouldn’t have shut down at the beginning But this is me saying that it is sad some of the problems we don’t even realize we have or will have because of the covid19 pandemic Much of the pandemic became a political issue which only hurts the patient when medical clarity is clouded by political preference.

It’s the JournalFeed Podcast for the week of Jan 11-15, 2021. We cover non-invasive ventilation for severe asthma, prognostication in near-hanging patients, push-dose phenylephrine for septic shock, safety bundles for critical pediatric intubation, and when to intubate patients with ACE inhibitor angioedema.

On todays podcast, I simplify the RAAS system and talk about how ACEi and ARBs work within the RAAS system to reduce vasoconstriction and sodium and water reabsorption. Let's Review!

FDA 批准促性腺激素释放激素（GnRH）拮抗剂治疗子宫肌瘤导致的大量子宫出血NEJM 比较子宫动脉栓塞术与子宫肌瘤切除术治疗子宫肌瘤的疗效Cell 在孕妇中利用代谢动力学预测孕周和分娩时间恶拉戈利（elagolix）恶拉戈利（elagolix）是一种口服促性腺激素释放激素（GnRH）拮抗剂，既往用于治疗子宫内膜异位症引起的盆腔疼痛。2020年5月，美国FDA批准恶拉戈利用于治疗绝经前期、子宫肌瘤导致的大量子宫出血。《UF-1和UF-2研究：恶拉戈利治疗子宫肌瘤所致月经过多的治疗方案》New England Journal of Medicine，2020年1月 (1)研究旨在比较恶拉戈利300mg bid（单药治疗或联合雌激素-孕激素反加疗法）对子宫肌瘤的疗效。在两项相同的试验（UF-1和UF-2）中，月经过多（月经失血量＞80 mL）且经超声诊断为子宫肌瘤的总共790名女性（平均年龄42岁）被随机分组，分别接受6个月的恶拉戈利联合反加疗法、恶拉戈利单药治疗或安慰剂治疗。研究者通过收集生理用品的方式量化月经失血量。两项研究6个月后，84%和77%的单药治疗、68.5%和76.5%的恶拉戈利联合反加疗法和9%的安慰剂组达到主要终点（月经量50%）。主要不良反应是潮热和子宫出血，恶拉戈利联合反加治疗组的发生率显著高于安慰剂组。反加治疗法减轻了恶拉戈利的低雌激素效应，腰椎骨密度减少0.76%，低于恶拉戈利单药治疗组2.95%。结论：恶拉戈利单药治疗或联合雌-孕激素反加疗法均有效减轻子宫肌瘤相关的月经过多。恶拉戈利单药治疗与骨密度显著降低相关，反加治疗可以减少这种副作用。子宫肌瘤子宫肌瘤，是女性最常见的盆腔肿瘤，是起源于子宫平滑肌细胞和成纤维细胞的单克隆非癌性肿瘤。主要发生在育龄期妇女，可表现为异常子宫出血、盆腔疼痛/压迫感、生殖功能障碍（不孕或产科并发症）。大多数的子宫肌瘤会在生产后或绝经后自行萎缩；如果子宫肌瘤引起严重症状，则需治疗。对没有生育要求的患者，可行宫腔镜下切除粘膜下肌瘤；雌-孕激素避孕药；释放孕激素的宫内节育器；氨甲环酸；促性腺激素释放激素（GnRH）的激动剂和拮抗剂等。对于有生育要求的患者，药物大多会妨碍受孕，因此治疗首选微创手术切除。《行子宫动脉栓塞术与子宫肌瘤切除术治疗子宫肌瘤的比较》New England Journal of Medicine，2020年7月 (2)对于希望保留子宫、且药物治疗无效的女性，子宫肌瘤切除术和子宫动脉栓塞术是可选治疗方案。这项多中心、随机、开放标签试验，旨在评估症状性子宫肌瘤患者中使用子宫肌瘤切除术和子宫动脉栓塞术的疗效的比较。子宫肌瘤切除术的可选术式包括开腹、腹腔镜或宫腔镜手术。研究共招募了254名女性随机分组：子宫肌瘤切除术组和子宫动脉栓塞术。随访2年时，两组的生活质量评分分别为84.6分和80.0分（P=0.01）。在所有初次手术中，子宫肌瘤切除术组29%的女性和子宫动脉栓塞术组24%的女性发生了围手术期和术后并发症。结论：在有症状的子宫肌瘤患者中，接受子宫肌瘤切除术的女性在2年时的子宫肌瘤相关生活质量优于接受子宫动脉栓塞术的女性。《随机双盲对照试验：术前氨甲环酸减少子宫肌瘤切除术失血》American Journal of Obstetrics and Gynecology，2020年9月(3)氨甲环酸是一种合成赖氨酸衍生物，具有抗纤溶活性，用于其他外科学科，以减少手术期间的失血。本研究旨在探讨早期静脉注射氨甲环酸对子宫肌瘤切除术妇女围手术期出血和输血需求的影响。这项双盲、随机、安慰剂对照试验中，纳入有大出血风险的、症状性子宫肌瘤的女性共60人，随机分入干预组（手术前20分钟静脉注射氨甲环酸15 mg/kg）和安慰剂组（手术前静脉注射生理盐水）。这里有大出血风险定义为：（1）至少1个肌瘤≥10cm，（2）任何1个肌壁内或阔韧带肌瘤≥6cm，和/或（3）手术前影像学检查提示至少有5个肌瘤。患者中53%接受腹腔镜子宫肌瘤切除术，40%接受机器人子宫肌瘤切除术，7%接受采用剖腹手术。氨甲环酸组和安慰剂组中，中位估计失血量分别为200ml和240ml（P=0.88）；中位手术时间没有差异（165min 和 164min），围手术期血红蛋白改变也没有差异（1.00 和 1.1 g/dL）。氨甲环酸组的患者均不需要输血，但安慰剂组有4例需要输血。结论：术前静脉给予氨甲环酸在腹腔镜或机器人肌瘤切除过程中，与减少出血量无关。《术前肠道准备并不能减少子宫切除术后的感染》American Journal of Obstetrics and Gynecology，2020年8月 (4)关于妇科手术前肠道准备的文献很少，在子宫切除术前进行肠道准备主要是借鉴结直肠手术的经验。因此本研究的目的是比较子宫切除术前，与无肠道准备相比，单纯机械性肠准备、单纯口服抗生素或联合使用抗生素是否与手术部位感染或吻合口漏发生率降低有关。研究回顾性的分析了10余年间、共224,687例子宫切除术手术患者的数据。其中良性疾病186,148例、平均45岁，恶性肿瘤38,539例，平均54岁。其中包括腹腔镜/机器人手术、剖腹手术和经阴道手术等不同术式。术前准备包括肠道准备、口服抗生素、两者联合等不同策略。研究人员发现，肠道准备并没有降低手术部位感染、吻合口漏或其他并发症的发病率。在恶性肿瘤、开腹子宫切除术中，肠道准备、口服抗生素或肠道准备联合抗生素等几种策略，与不进行抗生素预防治疗的患者相比，感染发病率没有差异。结论：无论手术方式如何，肠道准备都不能预防手术部位感染或并发症，可以安全省略此步骤。妊娠期高血压妊娠>20周的女性新发高血压，但没有蛋白尿或新发靶器官功能障碍，则诊断为妊娠期高血压。根据2019年美国妇产科医师学会的建议，无论是否有其他表现，收缩压≥ 160mmHg和/或舒张压≥110mmHg，应直接诊断为“重度子痫前期”，即以前所说的“重度妊娠高血压”。更名的原因是，即使没有蛋白尿，妊娠诱发的重度血压升高也可能导致严重的不良事件。若产后≥12周后，血压仍高于正常，诊断为慢性高血压。妊娠期高血压最常用的降压药物包括：甲基多巴、拉贝洛尔、硝苯地平。尚有争议的药物包括：噻嗪类利尿剂、肼屈嗪、可乐定、硝普钠。妊娠期应避免使用的药物包括：ACEI、ARB、直接肾素抑制剂、盐皮质激素。《综述：他汀类药物在预防子痫前期中的作用》American Journal of Obstetrics and Gynecology，2020年8月 (5)子痫前期的确切原因尚不清楚，但普遍认为与胎盘异常释放可溶性抗血管生成因子有关，加之氧化应激和炎症反应的增加，导致母体全身内皮功能障碍。他汀类药物已被证明可以纠正类似的病理生理过程。普伐他汀，在各种临床前期和临床研究中显示，它可以逆转妊娠特异性的血管功能失衡，恢复内皮健康，防止氧化和炎症损伤。人类研究表明普伐他汀具有良好的安全性，而最近的证据不支持他汀类药物致畸的担忧。结论：他汀类药物在子痫前期预防性的使用，仍需大型随机对照研究支持。《荟萃分析：口服降压药对慢性高血压孕妇的疗效和安全性的比较》American Journal of Obstetrics and Gynecology，2020年10月 (6)此荟萃分析的目的是同时比较降压药对患有慢性高血压的孕妇的疗效和安全性。共纳入了22项研究，包括4464名女性。随机对照试验的分析表明，没有任何药物会显著影响先兆子痫的发生率。与安慰剂相比，阿替洛尔与小于胎龄儿（small for gestational age，SGA）的风险增加显著相关（风险比 26.00），而且被列为疗效最差的降压药。严重高血压的发生率在以下药物的干预下显著降低：硝苯地平风险比0.27，甲基多巴风险比0.31，吲哚洛尔风险比0.29，酮舍林风险比0.17。相比而言，严重高血压发生的概率最高的药物包括：速尿、氨氯地平和安慰剂。硝苯地平和甲基多巴能显著降低胎盘早剥率的风险（风险比 0.29和0.23）。各类降压药在剖宫产、围产期死亡、早产和分娩时胎龄方面无显著差异。结论：阿替洛尔与小于胎龄儿的风险显著增加有关。当使用硝苯地平和甲基多巴时，严重高血压的发生率显著降低。尽管在降压药中先兆子痫的风险是相似的，但未来仍需大规模研究为妊娠期降压药的选择和目标血压提供指导。《前瞻性观察队列研究：慢性高血压患者妊娠并发症与妊娠前母体心脏功能和结构有关》American Journal of Obstetrics and Gynecology，2020年9月 (7)约3%的妊娠合并为慢性高血压，这些产妇的分娩并发症发生率可高达25 - 28%。本研究的目的是通过超声心动图，评估妊娠前孕妇的心脏结构和功能，寻找其与分娩并发症以及妊娠前治疗的相关性。这项前瞻性观察队列研究，纳入192名长期接受降压治疗的孕妇，妊娠前改用甲基多巴，并随访至分娩。在192例患者中，出现24例早期并发症（

The Filtrate:Matt SparksJoel TopfSwapnil HiremathJennie LinJordy CohenAnd two special guests:Morgan Grams, study author.Talar Kharadjian, nephrology fellow UC San DiegoShow Notes:History of albuminuria from Matt’s opening monolog: https://academic.oup.com/ndt/article/18/7/1281/1809803Microalbuminuria As A Predictor Of Clinical Nephropathy In Insulin-Dependent Diabetes Mellitus in the Lancet 1982.Microalbuminuria Predicts Clinical Proteinuria and Early Mortality in Maturity-Onset Diabetes in the NEJM 1984Episode of Freely Filtered with Dr. Feldman, the big guy at the top of the CRIC trial: NSAIDs vs Opioids.The Aldo study where they didn’t do a meta-analysis but they should have: Aldosteronism is everywhere.Estimating Urine Albumin-to-Creatinine Ratio from Protein-to-Creatinine Ratio: Development of Equations using Same-Day Measurements. Canadian data. CJASNThe kidney failure risk equation has a dotcom: https://kidneyfailurerisk.comKDIGO Controversies Conference on Early Identification & Intervention in CKDChoose Your Own Adventure: Cave of Time.Witte et al. in 2009 JASN on first morning urine vs 24 hour collection: First Morning Voids Are More Reliable Than Spot Urine Samples to Assess MicroalbuminuriaSensitivity and specificity for Joel to studyYour Manuscript On Peer ReviewNephrology Business Leaders University (NBLU)Cloth Masks May Prevent Transmission of COVID-19: An Evidence-Based, Risk-Based Approach with lead author Catherine Clasehttps://www.clothmasks.caElimination or Prolongation of ACE Inhibitors and ARB in Coronavirus Disease 2019 (REPLACECOVID)Fast Grant. Apparently they are not just for Brian ByrdNephJC ACE2 Stuff as Jordy calls it: http://www.nephjc.com/news/covidace2The BRACE-CORONA trial a 700 person RCT of ACEi and ARB in Covid-19. No effect. Tweet stream by Swapnil.MC Hammer is a science nerd: https://cen.acs.org/education/science-communication/Hammer-time-Science-Twitter-drummers/98/i31Hammerman origin story for the MC Hammer cartoon.Bowman Society Lecture - Race & Renal Function CalculationsBasic Research Forum for Emerging Kidney Scientists: A Partnership Between APS and ASN

Should patients with hypertension who are hospitalized due to COVID-19 continue to take angiotensin-converting enzyme inhibitors and angiotensin receptor blockers? Find out about this and more in today’s PV Roundup podcast.

Em entrevista à Panorama, Ari Klein diretor executivo da Associação Comercial de Itapejara D'Oeste, falou sobre como será a Itapevendas neste final de ano no município, e durante a entrevista destacou ainda as linhas de credito disponíveis para associados.

In this episode, we dive into the pharmacology of ACE inhibitors and ARBs, particularly understanding how they assist in preserving renal function in CKD and yet at the same time can harm the kidneys (e.g. cause AKI).

Editor's Summary by Howard Bauchner, MD, Editor in Chief of JAMA, the Journal of the American Medical Association, for the July 14, 2020 issue

Four observational studies regarding outcomes of COVID patients treated with ACEI and ARB were published in May 2020. More than 22,000 patients were analyzed at Bringham and Woman's Hospital, University of Milano, NYU Grossman School of Medicine, and the Cleveland Clinic with overall results that do not suggest continued use of ACE inhibitors or ARBs contribute to the severity of COVID 19 in patients.

Novel Coronavirus genome study underway.   Center for Infectious Disease Research and Policy say the pandemic  could last for 2 years.  Other updates on May 2, 2020.

Does ACEI/ARBS increase risk of COVID-19 complications?  Does Hydroxychloroquine lead to increased deaths?  COVID-19 updated for April 23.

Ve třinácté epizodě Kardiožurnálu zjistíte, zda má smysl vysazovat ACE inhibitory nebo sartany v době koronarovirové krize.

Topic: Care Transitions What are care transitions? -Acute to home or chronic care/step down -Example: Hospital to home Concern -Don’t want patient to return to the hospital within 30 days for same problem - Medicare refusal to pay for certain conditions to promote prevention Issues -Understand discharge orders -Comply with discharge orders -Drug coordination from pre-hospital, to in hospital, or post-hospital regimen -Labs and services to follow up Examples -Pneumonia & Serious infections – injectable to oral antibiotic, antibiotics compliance, monitor for symptoms (temperature, swelling, pain, GI symptoms, dizzy/confused, etc.) -Heart Failure – monitor weight everyday, comply with medicines -COPD/Emphysema – arrange for O2, use FiO2 to expand vital capacity, correct use of inhalers -Asthma – correct use of inhalers -Heart Attack – BP, lipid, ACEI regimen of medications – promote compliance -DVT – transition from injectable-to-oral anticoagulants – promote compliance, alert notification if bleed -Pain management – CDC recommendations Support -Nurse case managers -Pharmacists -Home – rest, anabolic diet, hydration ______ Make sure to subscribe to get the latest episode. Contact Us: Pharmacy Benefit News: http://www.propharmaconsultants.com/pbn.html Email: info@propharmaconsultants.com Website: http://www.propharmaconsultants.com/ Facebook: https://www.facebook.com/propharmainc Twitter: https://twitter.com/ProPharma/ Instagram: https://www.instagram.com/propharmainc/ LinkedIn: https://www.linkedin.com/company/pro-pharma-pharmaceutical-consultants-inc/ Podcast: https://anchor.fm/pro-pharma-talks

Dominate perioperative medication management with tips from Kashlak’s newly minted Chief of Perioperative Medicine, @aoglasser, Avital O’Glasser MD, FACP, FHM (OHSU). We cover perioperative anticoagulation, why “bridging is dead”, aspirin, dual antiplatelet therapy, DMARDS, diabetic medications, buprenorphine, and much more! Be sure to check out Dr. O’Glasser’s previous episode #135 Perioperative Medicine: Assess and Optimize Risk to get a full overview of perioperative medicine. ACP members can claim CME-MOC credit at https://www.acponline.org/curbsiders (CME goes live at 0900 ET on the episode’s release date).  Full show notes https://thecurbsiders.com/episode-list. Join our mailing list and receive a PDF copy of our show notes every Monday. Rate us on iTunes, recommend a guest or topic and give feedback at thecurbsiders@gmail.com. Credits Written and Produced by: Avital O’Glasser MD, FACP, FHM and Matthew Watto MD, FACP  CME Questions: Matthew Watto MD, FACP Infographic: Matthew Watto MD, FACP Cover Art: Kate Grant MBChB DipGUMed Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP  Editor: Matthew Watto MD, FACP Guest: Avital O’Glasser MD, FACP, FHM Time Stamps 00:00 Intro, disclaimer, guest bio 03:20 Guest one-liner 04:46 Picks of the Week*: A Moment of Lift (book) by Melinda Gates; Crawl (film); Rich Roll (podcast) episodes w/Valter Longo and David Sinclair 09:35 Avi’s mantras for perioperative management and other core tenants 14:40 NPO and The Consult Guys 17:23 Medical cannabis (marijuana) in perioperative medicine 19:24 Case #1 Ms. Bridge - perioperative anticoagulation: to bridge or not to bridge 25:00 Low bleeding risk surgeries and anticoagulation 27:25 Moderate to high bleeding risk surgeries and anticoagulation; What about the CHA2DS2 Vasc of 7? 28:42 Bridging for venous thromboembolism (VTE) 31:30 How to give instructions for holding warfarin 32:30 Bridging a DOAC 36:16 Recap on bridging VKAs and use of DOACs 37:48 Neuraxial anesthesia and anticoagulation 39:49 Biologic DMARDS; Nonbiologic DMARDS 43:48 Supplements and herbals 48:40 Case #1 wrap up 50:16 Case #2 -Mr. DAPT; Perioperative Aspirin; DAPT -dual antiplatelet therapy 57:20 Summary of perioperative antiplatelet therapy 63:18 Statins 64:45 Beta blockers 67:21 ACEI and ARB; Diuretics 69:17 Oral hypoglycemics and newer diabetes agents (SGLT2 inhibitors, GLP1 agonists); What about metformin? 72:04 Insulin 74:40 Case #2 wrap up 75:35 Case #3 Ms. GB Stone who takes lithium and buprenorphine 77:30 NSAIDS, Buprenorphine 81:45 ART, transplant meds, Lithium, MAOIs, Levothyroxine; Watch out for lithium 86:34 Case #3 wrap up 87:25 Take Home Points 88:45 Outro 90:15 Avi and Mr. Rogers  *The Curbsiders participates in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising commissions by linking to Amazon. Simply put, if you click on my Amazon.com links and buy something we earn a (very) small commission, yet you don’t pay any extra. Goals Listeners will develop a practical approach to perioperative medication management and review special considerations for the various drug classes. Learning objectives After listening to this episode listeners will... Frame perioperative medication management decisions as another type of patient-centered, surgery-specific perioperative “risk/benefit” decision Discuss guideline recommendations for the perioperative management of multiple classes of medications Examine more nuanced or challenging medications to manage in the perioperative setting Explore professional, patient-centered and multidisciplinary communication techniques when disagreements arise regarding best medication management recommendations Disclosures Dr O’Glasser reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.  Citation O’Glasser A, Williams PN, Watto MF. “#174 Perioperative Medication Management”. The Curbsiders Internal Medicine Podcast. https://thecurbsiders.com/episode-list. September 23, 2019.

Join Amina as she interviews Dr. Maryam Sharifian who visited and presented at IIIT during for the Summer Institute of Scholars in 2019. Dr. Sharifian talks about her study, "Trauma, Burnout, and Resilience of Syrian Primary Teachers Working Inside the War Zone". They discuss the findings from the study, the phenomenal resilience of teachers in the war zone in Syria, as well as the importance of teachers' well-being and how that plays a role in students' lives. Dr. Maryam Sharifian is an Assistant Professor at James Madison University, College of Education. Dr. Sharifian received her undergraduate and graduate degree in School Counseling from Tehran University in Iran. After completing her PhD in Early Childhood Education from SUNY at Buffalo, she started her position at JMU to teach undergraduate and graduate courses in Early Childhood Education. Dr. Sharifian serves as country liaison at Association for Childhood Education International (ACEI) as a National Representative (representing Iran/Middle East). She also served as Board of Directors of ACEI for three years. She is an active member in several international Early Childhood Organizations such as the World Organization for Early Childhood Education, Cooperative and International Education Society and American Education Research Association to advocate for children and teachers' right. Dr. Sharifian addresses educational issues relating to children and teachers in the area of armed conflict (their well-being and resilience strategies). In addition, she has worked with children of undocumented Afghan immigrants, school girls in rural Tanzania and street children in Iran. She has several book chapters and article publications related to teacher training and children education.

Join Amina as she interviews Dr. Maryam Sharifian who visited and presented at IIIT during for the Summer Institute of Scholars in 2019. Dr. Sharifian talks about her study, "Trauma, Burnout, and Resilience of Syrian Primary Teachers Working Inside the War Zone". They discuss the findings from the study, the phenomenal resilience of teachers in the war zone in Syria, as well as the importance of teachers' well-being and how that plays a role in students' lives. Dr. Maryam Sharifian is an Assistant Professor at James Madison University, College of Education. Dr. Sharifian received her undergraduate and graduate degree in School Counseling from Tehran University in Iran. After completing her PhD in Early Childhood Education from SUNY at Buffalo, she started her position at JMU to teach undergraduate and graduate courses in Early Childhood Education. Dr. Sharifian serves as country liaison at Association for Childhood Education International (ACEI) as a National Representative (representing Iran/Middle East). She also served as Board of Directors of ACEI for three years. She is an active member in several international Early Childhood Organizations such as the World Organization for Early Childhood Education, Cooperative and International Education Society and American Education Research Association to advocate for children and teachers' right. Dr. Sharifian addresses educational issues relating to children and teachers in the area of armed conflict (their well-being and resilience strategies). In addition, she has worked with children of undocumented Afghan immigrants, school girls in rural Tanzania and street children in Iran. She has several book chapters and article publications related to teacher training and children education.

Jacques Latour, directeur chargé des technologies et de la sécurité à l’ACEI, présente le pare-feu DNS et les solutions technologiques qu'il offre aux utilisateurs à l'échelle du pays.

In this episode we cover what I think it game time ready about our beloved ACEI and then Joe and I talk about 3 articles that you need to know including the new seizure medication just approved by the FDA.

Opiates vs nonopiates for chronic arthritic pain, TXA for epistaxis in patients taking antiplatelet drugs, clinical bundles to reduce hypoxia in prehospital intubation, peripheral catheters in the ED (really needed?), flecainide for chemical cardioversion of AF, HEMS for head trauma patients, treatment of Cannabinoid hyperemesis syndrome, ACEI induced visceral angioedema, Prehospital EtCO2 and mortality, detecting critical illness in drunk patients, Opioid prescribing in the ED, Naproxen with or without muscle relaxants for acute low back pain, reviews of TIA and sudden onset headache evaluation and management in the ED.

Join us on todays share to discuss FGM, child marriage, early marriage and other forms of GBV.. Why  do these forms of abuse persist and much more...Todays special guest Alimatu Dimonekene Who is Alimatu? Alimatu Dimonekene has dedicated her life to stopping FGM as well as other violent and exploitative practices toward women and girls, both here in the UK and across the globe. Winner of the True Hero Award 2015 for her work in tackling FGM, Alimatu has used her experiences as an FGM survivor in working extensively with key agencies, including UN Women (UK), The Home Office, Metropolitan Police, NHS and the NSPCC.  Alimatu has also worked with a number of respected authorities and media partners that are dedicated to safeguarding girls and women at risk. She plans to extend her work and become much more active in Sierra Leone, the Democratic Republic of the Congo and Liberia – supporting communities with strategies for eliminating violence against women and girls. In December 2015, Alimatu was invited by the African Union to host Youth Panel discussions at the End Child Summit in Lusaka, Zambia – in order to look at ways of combating Child and Early Marriage worldwide. Alimatu made such an impact that she is now mentoring most of the Youth delegates she met at the Summit. ProjectACEi will not rest until the whole world has ended the practice of Female Genital Mutilation (FGM).Tune in, Skype in, Call in, Chat in and Let's Talk!

One in four heart failure patients are readmitted within 30 days of hospital discharge...often due to medication-related problems. But early follow-up from you...their pharmacist...can help. For example, talking with patients within 2 days of discharge PLUS an office visit within 7 days prevents one ED visit for every 9 heart failure patients...and one readmission for every 52 patients. Expect to see more hospitals, prescribers, and payers looking to work with YOU to help reduce readmissions. Your expertise can improve care...and save money. Think of your role managing heart failure as similar to managing anticoag patients. There'll be professional and financial opportunity in it. Offer comprehensive med reviews to identify and resolve problems. Recommend an ACEI or ARB plus an "evidence-based" beta-blocker...bisoprolol, carvedilol, or metoprolol SUCCINATE...for systolic heart failure. Suggest adding an aldosterone antagonist if symptoms persist. Recommend trying to titrate to target doses that improve survival, such as lisinopril 20 to 40 mg/day or metoprolol succinate 200 mg/day. Consider suggesting Entresto (sacubitril/valsartan) instead of the ACEI or ARB if hospitalization occurs despite use of target doses. But be aware of hypotension, and avoid Entresto when systolic BP < 100 mmHg. Educate patients about self-management...and when to get help. Include caregivers...they are crucially important to success in many cases. Consider using a heart failure questionnaire from our PL Detail-Document to identify red flags BEFORE patients get worse. For example, advise patients to report if weight changes by more than a few pounds. Emphasize adherence with meds, limiting fluids, diet, etc. For example, help patients understand how taking their ACEI or ARB improves their outcomes. Plus this also impacts Star Ratings. Suggest pillboxes or consider offering med sync to boost adherence. Use our PL Conversation Starter to guide your discussions. Communicate with colleagues if you find problems with med lists or identify adherence issues...to prevent gaps in therapy.

Commentary by Dr. Valentin Fuster

In this VetGirl podcast, we review initial treatment of chronic Lyme nephritis, focusing specifically on antihypertensive therapy, ACEi therapy, nutritional support, and possible immunosuppressive therapy. For chronic Lyme disease, appropriate monitoring for proteinuria or microalbuminuria should be performed q. 3-6 months. In patients that have continued proteinuria (after 4-6 weeks of antibiotic therapy), a renal biopsy should be considered (to rule out an immune-mediated glomerulonephritis), along with a low-protein diet, angiotensin-converting enzyme inhibitor (ACEi) therapy, and an additional course of antibiotic therapy. If evidence of immune-mediated glomerulonephritis is seen, the use of immunosuppressive therapy is warranted (e.g., azathioprine, cyclosporine, mycophenolate, etc.).

In this VetGirl podcast, we review initial treatment of chronic Lyme nephritis, focusing specifically on antihypertensive therapy, ACEi therapy, nutritional support, and possible immunosuppressive therapy. For chronic Lyme disease, appropriate monitoring for proteinuria or microalbuminuria should be performed q. 3-6 months. In patients that have continued proteinuria (after 4-6 weeks of antibiotic therapy), a renal biopsy should be considered (to rule out an immune-mediated glomerulonephritis), along with a low-protein diet, angiotensin-converting enzyme inhibitor (ACEi) therapy, and an additional course of antibiotic therapy. If evidence of immune-mediated glomerulonephritis is seen, the use of immunosuppressive therapy is warranted (e.g., azathioprine, cyclosporine, mycophenolate, etc.).

In this VetGirl podcast, we review initial treatment of chronic Lyme nephritis, focusing specifically on fluid therapy and gastrointestinal support. For chronic Lyme disease, appropriate monitoring for proteinuria or microalbuminuria should be performed q. 3-6 months. In patients that have continued proteinuria (after 4-6 weeks of antibiotic therapy), a renal biopsy should be considered (to rule out an immune-mediated glomerulonephritis), along with a low-protein diet, angiotensin-converting enzyme inhibitor (ACEi) therapy, and an additional course of antibiotic therapy. If evidence of immune-mediated glomerulonephritis is seen, the use of immunosuppressive therapy is warranted (e.g., azathioprine, cyclosporine, mycophenolate, etc.).

In this VetGirl podcast, we review initial treatment of chronic Lyme nephritis, focusing specifically on fluid therapy and gastrointestinal support. For chronic Lyme disease, appropriate monitoring for proteinuria or microalbuminuria should be performed q. 3-6 months. In patients that have continued proteinuria (after 4-6 weeks of antibiotic therapy), a renal biopsy should be considered (to rule out an immune-mediated glomerulonephritis), along with a low-protein diet, angiotensin-converting enzyme inhibitor (ACEi) therapy, and an additional course of antibiotic therapy. If evidence of immune-mediated glomerulonephritis is seen, the use of immunosuppressive therapy is warranted (e.g., azathioprine, cyclosporine, mycophenolate, etc.).

Tina revisits ACEI, ARB, BB, and Thiazides, which were covered previously with the hypertension episodes, and introduces a few new medications as well: Mineralocorticoid Receptor Antagonists: spironolactone and eplerenone Loop diuretic: furosemide Digoxin Vasodilators: hydralazine and isosorbite dinitrate For a quick summary of the CCS 2013 recommendations: ACE inhibitors: all asymptomatic patients with an EF […] The post CHF 2: medications appeared first on Family Pharm Podcast.

We reviewed some evidence on the treatment of hypertension that are contradictory to the CHEP 2013 guidelines summarized in our previous episodes. Salt restriction for hypertension CHEP 2013: 1500 mg of sodium per day is recommended for adults age 50 years or less; 1300 mg per day if age 51 to 70 years; and 1200 mg […] The post Hypertension 4: EBM Special appeared first on Family Pharm Podcast.

Background: Blood pressure lowering drugs are usually evaluated in short term trials determining the absolute blood pressure reduction during trough and the duration of the antihypertensive effect after single or multiple dosing. A lack of persistence with treatment has however been shown to be linked to a worse cardiovascular prognosis. This review explores the blood pressure reduction and persistence with treatment of antihypertensive drugs and the cost consequences of poor persistence with pharmaceutical interventions in arterial hypertension. Methods: We have searched the literature for data on blood pressure lowering effects of different antihypertensive drug classes and agents, on persistence with treatment, and on related costs. Persistence was measured as patients' medication possession rate. Results are presented in the form of a systematic review. Results: Angiotensin II receptor blocker (ARBs) have a competitive blood pressure lowering efficacy compared with ACE-inhibitors (ACEi) and calcium channel blockers (CCBs), beta-blockers (BBs) and diuretics. 8 studies describing the persistence with treatment were identified. Patients were more persistent on ARBs than on ACEi and CCBs, BBs and diuretics. Thus the product of blood pressure lowering and persistence was higher on ARBs than on any other drug class. Although the price per tablet of more recently developed drugs (ACEi, ARBs) is higher than that of older ones (diuretics and BBs), the newer drugs result in a more favourable cost to effect ratio when direct drug costs and indirect costs are also considered. Conclusion: To evaluate drugs for the treatment of hypertension several key variables including the blood pressure lowering effect, side effects, compliance/persistence with treatment, as well as drug costs and direct and indirect costs of medical care have to be considered. ARBs, while nominally more expensive when drug costs are considered only, provide substantial cost savings and may prevent cardiovascular morbidity and mortality based on the more complete antihypertensive coverage. This makes ARBs an attractive choice for long term treatment of hypertension.