Podcasts about nstemi

Vijay Kunadian talks to C. Michael Gibson about using an invasive or conservative strategy for older patients with NSTEMI.

N Engl J Med 2024;391:1673-1684Background: Non-ST elevation myocardial infarction (NSTEMI) is the most common acute coronary syndrome subtype in adults over 75 years old. However, these patients were underrepresented in landmark NSTEMI trials. Older adults with multiple comorbidities face an increased risk of mortality. While NSTEMI contributes to this risk, they also have competing risks such as advanced age, frailty, and chronic kidney disease. The presence of competing risks means that aggressively managing one condition may have a smaller impact on overall mortality compared to a younger, otherwise healthy adult with myocardial infarction, whose primary risk of death stems from the myocardial infarction itself. Additionally, comorbid conditions like advanced kidney disease and diffuse atherosclerosis can increase the risks associated with revascularization.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.A patient-level meta-analysis of smaller trials, including 1,479 patients, found that in elderly patients with NSTEMI, an invasive strategy reduced myocardial infarction and urgent revascularization but not mortality.The Older Patients with Non–ST-Segment Elevation Myocardial Infarction Randomized Interventional Treatment (SENRIOR-RITA) trial sought to assess invasive vs conservative management of elderly patients with NSTEMI, in a more pragmatic design.Patients: Eligible patients had to have type I NSTEMI and be 75 years or older.Patients were excluded if they had cardiogenic shock or life expectancy less than 1 year.Baseline characteristics: The trial randomized 1,518 patients from hospitals across England and Scotland – 753 randomized to invasive strategy and 765 to conservative strategy.The average age of patients was 82 years and 55% were men. Approximately 65% had hypertension, 31% had diabetes, 31% had hyperlipidemia, 31% had prior myocardial infarction, 15% had prior stroke or TIA, 21% had kidney disease, 15% had chronic obstructive pulmonary disease, and 5% were current smokers.The average Charlson comorbidity index was 5.Procedures: Patients were randomly assigned in a 1:1 ratio to undergo invasive or conservative strategy.In the invasive strategy, patients underwent coronary angiogram, and revascularization was performed as appropriate. In the conservative arm, patients were treated (unless contraindicated) with aspirin, a P2Y12 receptor antagonist, statin, beta-blocker and an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker. Patients in the conservative arm were allowed to have a coronary angiogram if they had worsening clinical status.Endpoints: The primary end point was a composite of cardiovascular death or nonfatal myocardial infarction. Secondary outcomes included all-cause death, subsequent coronary revascularization, hospitalization for heart failure, stroke and bleeding.Analysis was performed based on the intention-to-treat principle. The trial aimed to detect a hazard ratio of 0.78, assuming a 20% risk of the primary outcome in the conservative arm. A sample size of 1,668 patients with at least 688 primary outcome events would provide 90% power at 5% alpha, while 520 events would provide 80% power.Results: Among the patient randomized to the invasive arm, 90% underwent coronary angiography and 50% underwent revascularization. The medium number of days from admission to coronary angiography was 5. Among patients randomized to the conservative arm, 5.6% underwent coronary angiography within 7 days. The median follow-up time was 4.1 years.The primary outcome was not significantly different between both groups (25.6% with invasive vs 26.3% with conservative, HR: 0.94, 95%: 0.77 - 1.14; p= 0.53).There was also no difference in all-cause death (36.1% vs 32.3%), cardiovascular death (15.8% vs 14.2%), stroke (4.2% vs 5.2%), hospitalization for heart failure (10.9% vs 10.7%), or major bleeding (8.2% vs 6.4%) “incidence for invasive mentioned first”. Future coronary revascularization was more frequent in the conservative arm (13.7% vs 3.9%). Non-fatal myocardial infarction was significantly lower with an invasive strategy (11.7% vs 15.0%).Procedural related complications occurred in less than 1% of the patients.There were no significant subgroup interactions for the primary outcome.Conclusion: In older patients with NSTEMI, an invasive strategy compared to conservative strategy, did not reduce the primary composite endpoint of cardiovascular death or nonfatal myocardial infarction, over a median of 4.1 years.The trial enrolled fewer patients than planned, and the lower-than-expected event rate reduced its statistical power. Additionally, the median 5-day delay before coronary angiography may have biased the results toward the conservative strategy.Despite its limitations, this trial demonstrates that a conservative approach is a reasonable option for selected older patients with NSTEMI. It also highlights that, although enrolling older patients with comorbidities in trials is challenging, it is feasible, and greater effort is needed to include more of this population in future trials.Finally, in this trial of patients with myocardial infarction, about one-third died over a median of 4.1 years, with less than half of these deaths attributed to cardiovascular disease. Even if an invasive strategy had reduced cardiovascular mortality, its impact on all-cause mortality would have been less significant. This concept extends beyond this trial; when interventions are applied to older patients with multiple competing risks, their overall benefit diminishes.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

JAMA Intern Med 2023;183:407-415Background: As we have previously discussed, trials comparing invasive versus conservative management in patients with non-ST elevation myocardial infarction (NSTEMI) have yielded mixed results. The average age of participants in these studies was in the 60s, and multiple comorbidities were relatively uncommon. However, many NSTEMI patients seen in clinical practice are older and have multiple comorbidities. These patients have worse prognosis and have competing risks for mortality. Whether an invasive strategy provides a benefit for this population remains uncertain.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 MOSCA-FRAIL trial sought to compare invasive vs conservative strategy in older adults with frailty and NSTEMI.Patients: Eligible patients had to have NSTEMI, be 70 years or older, and have frailty defined by 4 points or greater on the Clinical Frailty Scale.Patients were excluded if they were known to have nonrevascularizable coronary artery disease, significant concomitant non-ischemic heart disease, or life expectancy less than 12 months.Baseline characteristics: The trial randomized 167 patients from 13 hospitals in Spain – 84 randomized to invasive strategy and 83 to conservative strategy.The average age of patients was 86 years and 47% were men. Approximately 92% had hypertension, 56% had diabetes, 77% had hyperlipidemia, 31% had prior myocardial infarction, 27% had history of atrial fibrillation, 18% had prior stroke, 44% had chronic kidney disease, and 3% were current smokers.Procedures: Patients were randomly assigned in a 1:1 ratio to undergo invasive or conservative strategy.In the invasive strategy, patients underwent coronary angiogram within 72 hours of admission, and revascularization was performed as appropriate. In the conservative arm, patients were treated with medical therapy alone. A coronary angiogram was permitted for recurrent ischemia during the index admission.Medical treatment was given according to the guidelines at the time. In both arms, dual antiplatelet was recommended for one year. In patients with high bleeding risk or taking an oral anticoagulant, one antiplatelet could be stopped after the first month.Endpoints: The primary end point was the number of days alive and out of the hospital between discharge from the index hospitalization to 1 year. The coprimary end point was the composite of cardiac death, reinfarction, or post-discharge revascularization.Analysis was performed based on the intention-to-treat principle. The estimated sample size to provide 80% power at 5% alpha was 176 patients. This assumed that the number of days for the primary outcome in the conservative arm was 273 days and that an invasive strategy would increase that by 20%, that is 55 days.Results: Due to the COVID pandemic, the trial was terminated early after randomizing 95% of the planned sample size. During the index admission, 98% of the patients in the invasive arm underwent coronary angiogram and 60% underwent revascularization. Among patients in the conservative arm, 9.6% underwent revascularization due to recurrent ischemia during the index admission.The primary outcome (number of days alive and out of the hospital between discharge from the index hospitalization to 1 year) was numerically lower with the invasive arm but this was not statistically significant (mean difference 28 days, 95% CI: -7 – 62; p= 0.12).There was no difference in the coprimary end point - cardiac death, reinfarction, or post-discharge revascularization – absolute values were not provided. The invasive strategy was associated with significantly more bleeding events requiring hospitalization (8 patients vs 1 patient, incidence rate ratio: 14.9, 95% CI: 1.7 – 129.0; p= 0.02) including 4 deaths related to bleeding.Conclusion: In older, frail patients with NSTEMI, an invasive strategy did not significantly reduce the number of days of being alive and out of the hospital at 1-year. It also did not reduce the coprimary end point which was the composite of cardiac death, reinfarction, or post-discharge revascularization. An invasive strategy was associated with more bleeding requiring hospitalization.The trial is small, and its results should be interpreted with caution. Nonetheless, it is an important study that paves the way for future, larger trials in this population. The primary endpoint is both meaningful and relevant to this population. The average age of participants in this trial is approximately 20 years older than those in TACTICS-TIMI 18, RITA 3, and ICTUS. It is important to recognize that older, frail patients with multiple comorbidities are significantly underrepresented in clinical trials and likely derive less benefit or even harm from interventions.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. 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N Engl J Med 2005;353:1095-1104Background: Prior trials on revascularization in patients with acute coronary syndromes without ST-segment elevation have yielded mixed results. While FRISC II and TACTICS-TIMI 18 demonstrated a significant reduction in myocardial infarction, this benefit was not observed in RITA 3. None of these trials showed a significant reduction in mortality. Further research is needed to guide treatment strategies in this population, particularly after the introduction of early use of clopidogrel and intensive lipid-lowering 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 Invasive versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS) trial sough to test the hypothesis that an early invasive strategy is superior to selective invasive strategy for patients with non-ST elevation myocardial infarction (NSTEMI).Patients: Eligible patients had to have all of the following: Worsening symptoms of ischemia or symptoms at rest with the last episode being 24 hours before randomization, elevated cardiac troponin T level (≥0.03 μg per liter); and either ischemic EKG changes (defined as ST-segment depression or transient ST-segment elevation exceeding 0.05 mV, or T-wave inversion of ≥0.2 mV in two contiguous leads) or a documented history of coronary artery disease.Patients were excluded if they were older than 80 years, had an indication for primary percutaneous coronary intervention or fibrinolytic therapy, hemodynamic instability or overt congestive heart failure, oral anticoagulant drugs use in the past 7 days, fibrinolytic treatment within the past 96 hours, percutaneous coronary intervention within the past 14 days, elevated bleeding risk, plus others.Baseline characteristics: The trial randomized 1,200 patients from 42 Dutch hospitals – 604 randomized to early invasive strategy and 596 randomized to selective invasive strategy.The average age of patients was 62 years and 74% were men. Approximately 39% had hypertension, 14% had diabetes, 35% had hyperlipidemia, 23% had prior myocardial infarction and 41% were current smokers.Approximately 48% of the patients had ST deviation equal to or greater than 0.1 mV.Procedures: Patients were randomly assigned in a 1:1 ratio to undergo early invasive vs selective invasive strategy.Patients received 300 mg of aspirin at the time of randomization, followed by at least 75 mg daily indefinitely, and enoxaparin (1 mg/kg for a maximum of 80 mg) subcutaneously twice daily for at least 48 hours. The early use of clopidogrel (300 mg immediately, followed by 75 mg daily) in addition to aspirin was recommended to the investigators after the drug was approved for acute coronary syndrome in 2002. Intensive lipid-lowering therapy, preferably atorvastatin 80 mg daily or the equivalent was recommended as soon as possible after randomization. All interventional procedures during the index admission were performed with the use of abciximab.Patients assigned to the early invasive strategy were scheduled to undergo angiography within 24 - 48 hours after randomization. Patients assigned to the selective invasive strategy underwent coronary angiography if they had refractory angina despite optimal medical therapy, hemodynamic or rhythm instability, or significant ischemia on pre-discharge exercise test.In both groups, percutaneous coronary intervention (PCI) was performed when appropriate, without providing more details in the manuscript.The level of creatine kinase MB was measured at 6-hour intervals during the first day, after each new clinical episode of ischemia, and after each percutaneous revascularization procedure.Endpoints: The primary endpoint was a composite of all-cause death, myocardial infarction, or rehospitalization for angina at 1-year.The estimated sample size to provide 80% power to detect 25% relative risk difference between the two treatment groups at 5% alpha was 1,200 patients. This assumed that 21% of the patients in the early invasive arm would experience the primary outcome.Results: During the index admission, 98% of the patients in the early invasive strategy arm underwent coronary angiogram compared to 53% in the selective invasive arm. At 1-year, 79% of the patients in the early invasive strategy arm underwent revascularization compared to 54% in the selective invasive arm.The primary outcome was not significantly different between both treatment groups (22.7% with early invasive vs 21.2% with selective invasive, RR: 1.07; 95% CI: 0.87 - 1.33; p= 0.33). All-cause death was the same in both groups (2.5%). Myocardial infarction was significantly higher with the early invasive strategy (15.0% vs. 10.0%, RR: 1.50, 95% CI: 1.10 – 2.04; p= 0.005), while rehospitalization for angina was lower with early invasive (7.4% vs. 10.9%, RR: 0.68, 95% CI: 0.47 – 0.98; p= 0.04). Most myocardial infarctions were revascularization related and these were significantly more frequent with early invasive (11.3% vs 5.4%). Spontaneous myocardial infarctions were 3.7% with early invasive and 4.6% with selective invasive and this was not statistically significant.Major bleeding, not related CABG, during the index admission was more frequent with the early invasive strategy (3.1% vs 1.7%).There were no significant subgroup interactions for the primary outcome, including based on ST deviation and troponin levels.Conclusion: In patients with NSTEMI, an early invasive strategy was not superior to selective invasive strategy in reducing the composite endpoint of all-cause death, myocardial infarction, or rehospitalization for angina at 1-year. An early invasive strategy was associated with more myocardial infarctions with a number needed to harm of 20 patients, which was secondary to revascularization related myocardial infarction. An early invasive strategy reduced rehospitalization for angina with a number needed to treat of approximately 29 patients.The ICTUS trial showed that revascularization can cause harm and highlighted how counting procedural myocardial infarctions can influence outcome estimates. While there is ongoing debate about the significance of periprocedural myocardial infarctions, evidence indicates an association with increased mortality. Whether periprocedural myocardial infarctions are 'less severe' than spontaneous myocardial infarctions remains controversial, as their impact varies based on infarct size and patient characteristics. This underscores the importance of including all-cause mortality or advanced systolic heart failure as endpoints in trials of revascularization.Patients in ICTUS received better background medical therapy compared to prior trials in this area. While this could be responsible for the divergent results compared to other prior trials. It also highlights the heterogeneity of NSTEMI patients and that an invasive strategy is not appropriate for all.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

The Lancet 2002;360:743-751Background: The TACTICS-TIMI 18 trial showed that an early invasive strategy in beneficial in selected patients with unstable angina or non-ST-elevation myocardial infarction (NSTEMI). These positive findings contrasted the findings from some earlier studies.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 British Heart Foundation RITA 3 randomized trial sought to compare invasive vs conservative strategy in patients with unstable angina or NSTEMI, similar to the trial question of TACTICS-TIMI 18.Patients: Eligible patients had suspected cardiac chest pain at rest with at least one of the following: Evidence of ischemia on electrocardiogram (ST depression, transient ST elevation, old left bundle branch block, or T wave inversion), pathologic Q waves suggesting previous myocardial infarction, or documented coronary artery disease on prior coronary angiogram.Patients were excluded if they had evolving myocardial infarction in which reperfusion therapy was indicated. Patients were also excluded if creatine kinase or creatine kinase MB concentrations were twice the upper limit of normal before randomization, if they had myocardial infarction within a month, had percutaneous coronary intervention (PCI) in the previous 12 months, or coronary artery bypass grafting (CABG) at any time.Baseline characteristics: The trial randomized 1,810 patients – 895 randomized to the invasive strategy and 915 randomized to conservative strategy. Patients were recruited from 45 hospitals in England and Scotland.The average age of patients was 63 years and 62% were men. Approximately 35% had hypertension on drugs, 13% had diabetes and 28% had prior myocardial infarction.The majority (92%) of the patients were enrolled because they met the criteria for evidence of ischemia on electrocardiogram.Procedures: Patients were randomly assigned in a 1:1 ratio to undergo invasive vs conservative strategy.In the conservative arm, patients received aspirin and enoxaparin 1mg/kg subcutaneously twice a day for 2-8 days. Beta-blockers, other antiplatelets and glycoprotein IIb/IIIa inhibitors could also be used. Coronary angiography could be performed if patients had anginal symptoms at rest or with minimal exertion despite appropriate therapy or if they had ischemia on stress testing.Patients in the invasive strategy arm received similar medical therapy to the conservative arm. Coronary angiogram was to be performed as soon as possible after randomization and ideally within 72 hours. Revascularization was recommended for lesions of at least 70% stenosis or 50% or more if left main.Endpoints: The trial had two co-primary outcomes. The first was a composite of death from any cause, nonfatal myocardial infarction, or refractory angina at 4 months. The second was a composite of death from any cause or nonfatal myocardial infarction at 1 year.Analysis was performed based on the intention-to-treat principle. The estimated sample size to provide 80% power at 5% alpha, was 1,770 patients. This assumed that 12% of the patients in the conservative arm would experience the outcome of death or non-fatal myocardial infarction at 1-year, and that the invasive strategy would result in 33% relative risk reduction in this outcome.Results: In the invasive strategy, 97% of the patients underwent coronary angiogram at a median of 2 days after randomization, and 55.3% underwent PCI or CABG. In the conservative arm, 10.3% had revascularization during the index admission, and 17.3% had revascularization at 1-year. The median follow time was 2 years and 97% of the patients had at least 1-year of follow up.The first primary composite outcome of death from any cause, nonfatal myocardial infarction, or refractory angina at 4 months was lower with the invasive strategy (9.6% vs 14.5%, HR: 0.66, 95% CI: 0.51 – 0.85; p= 0.001). The second primary composite outcome of death from any cause or nonfatal myocardial infarction at 1 year was not significantly different between both groups (7.6% with invasive vs 8.3% with conservative, HR: 0.91, 95% CI: 0.67 – 1.25; p= 0.58). At 1-year, 4.6% patients died in the invasive arm compared to 3.9% in the conservative arm, and this was not statistically significant. Myocardial infarction at 1-year occurred in 3.8% of the patients in the invasive arm compared to 4.8% in the conservative arm, and this was not statistically significant as well.All bleeding occurred in 8.2% in the invasive arm and 3.5% in the conservative arm.Subgroup analysis showed that men benefited from an invasive strategy while women did not (p for interaction= 0.011). The endpoint of death or myocardial infarction at 1-year, in women, was 5.1% in the conservative arm and 8.6% in the invasive arm, while in men, the incidence of this endpoint was 10.1% in the conservative arm and 7.0% in the invasive arm.Conclusion: In patients with unstable angina or NSTEMI, an invasive strategy compared to conservative strategy, reduced refractory angina but not myocardial infarction or death at 1-year.The reduction in angina is a subjective endpoint, prone to bias and faith healing, as we have previously discussed in other trials of PCI. The reduction in this endpoint alone should not justify widespread adoption of invasive strategy for unstable angina or NSTEMI.A key distinction between this trial and TACTICS-TIMI 18—which demonstrated a reduction in myocardial infarction with an invasive approach—is that this study included patients with smaller myocardial infarctions. Only 41% of participants had ST depression or transient ST elevation, and patients were excluded if creatine kinase or creatine kinase MB levels were more than twice the upper limit of normal before randomization. This highlights the heterogeneity among patients with unstable angina and NSTEMI, where baseline risk and the extent of myocardial necrosis influence treatment effects. We encourage you to read again the subgroup interactions of TACTICS-TIMI 18.Additionally, in the current era, high-sensitivity troponin assays enable the detection of smaller myocardial infarctions, potentially limiting the applicability of older trial results to all present NSTEMI 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. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

N Engl J Med 2001;344:1879-1887Background: Acute coronary syndrome is broadly categorized into unstable angina, non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI). In unstable angina, there is no rise in cardiac biomarkers, although some challenge this clinical entity in the current era of high sensitivity troponins. In NSTEMI, there is elevation of cardiac biomarkers but no ST segment elevation on the electrocardiogram. In STEMI, there is an ST segment elevation on the electrocardiogram as well as a rise in cardiac biomarkers.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.In patients with STEMI, percutaneous coronary intervention (PCI) significantly improves outcomes. However, its role in acute coronary syndrome without ST-segment elevation is less clear for several reasons. Patients with NSTEMI tend to be older and have more comorbidities, increasing procedural risks. This also means that they have competing risks for mortality, potentially reducing the benefit of PCI. Another key challenge is that NSTEMI patients frequently have multivessel disease, making it more difficult to identify the culprit lesion; since there is usually only partial occlusion of the culprit coronary artery. In contrast, there is usually complete occlusion of a coronary artery in STEMI and ST-segment elevation on the electrocardiogram helps localize the infarcted area, making it relatively easy to identify the culprit artery.The findings from previous randomized trials of revascularization in unstable angina and NSTEMI, have been inconsistent. The TACTICS–Thrombolysis in Myocardial Infarction 18 trial sought to compare early invasive vs conservative strategy in patients with unstable angina or NSTEMI.Patients: Eligible patients had angina within 24 hours that was: >20 minutes in duration, accelerating angina, or recurrent episodes at rest or with minimal effort. Patients also had to have one of the following: ST-segment depression of at least 0.05 mV, transient ( 2.5 mg/dL.Baseline characteristics: The trial randomized 2,220 patients – 1,114 randomized to early invasive strategy and 1,106 randomized to conservative strategy.The average age of patients was 62 years and 66% were men. Approximately 28% had diabetes and 39% had prior myocardial infarction.Troponin T levels were elevated (>0.01 ng/ml) in 54% of the patients.Procedures: Patients were randomly assigned in a 1:1 ratio to undergo early invasive vs conservative strategy.Patients received aspirin 325 mg daily, intravenous unfractionated heparin (5000U bolus, followed by an infusion at 1000U/ hour for 48 hours), and intravenous tirofiban (0.4 μg/kg/minute for 30 minutes followed by an infusion of 0.1 μg/kg/minute for 48 hours or until revascularization with tirofiban administered for at least 12 hours after PCI).Patients in the early invasive arm underwent coronary angiogram between 4 and 48 hours after randomization and underwent PCI as appropriate. Patients in the conservative arm were treated medically. If stable, they underwent an exercise-tolerance test before discharged (83% of these tests were with nuclear perfusion or echocardiography imaging). Patients in the conservative arm underwent coronary angiography with PCI if they had angina at rest associated with ischemic EKG changes or elevation in cardiac biomarkers, had clinical instability or had ischemia on their stress test.Endpoints: The primary outcome was a composite of death from any cause, nonfatal myocardial infarction, and rehospitalization for an acute coronary syndrome, at six months.The estimated sample size to provide 80% power was 1,720 patients. This assumed that 22% of the patients in the conservative arm would experience the primary outcome and that the early invasive strategy would result in 25% relative risk reduction in the primary outcome. The sample size was later increased to 2,220 patients.Results: In the early invasive strategy, 97% of the patients underwent coronary angiogram after a medium of 22 hours after randomization, and 60% underwent PCI or CABG. In the conservative arm, 51% underwent coronary angiogram and 36% underwent revascularization during the index hospitalization.The primary composite endpoint was lower with the early invasive strategy (15.9% vs 19.4%, odds ratio: 0.78, 95% CI: 0.62 - 0.97; p= 0.025). The Kaplan-Meier curves started to separate at approximately one week. This benefit was driven by lower myocardial infarction and lower rehospitalization for an acute coronary syndrome with the early invasive strategy; (4.8% vs 6.9%) and (11.0% vs 13.7%), respectively. There was no difference in all-cause death (3.3% vs 3.5%).There were 3 important subgroup interactions. First is based on ST changes where patients with ST changes at presentation had all the benefit with an early invasive strategy (16.4% vs 26.3% [for patients with ST changes] and 15.6% vs 15.3% [for patients without ST changes]). Second is based on Troponin T levels where patients with troponin T> 0.1 ng/mL had significantly more benefit with an early invasive strategy (16.4% vs 24.5% and 15.1% vs 16.6%). The third is based on TIMI score where patients with higher TIMI score had more benefit with an early invasive approach. For a high TIMI score of 5-7, the event rate was 19.5% with early invasive vs 30.6% with conservative approach. Patients with TIMI score of 0-2 had no benefit with an early invasive strategy (12.8% with early invasive vs 11.8% with conservative strategy).Note to readers: TIMI score is a risk stratification tool used to predict 14-day adverse outcomes in patients with unstable angina or NSTEMI. The score ranges from 0 to 7 with higher scores indicating worse prognosis.Conclusion: In patients with unstable angina or NSTEMI, an early invasive strategy reduced the composite endpoint of death from any cause, nonfatal myocardial infarction, and rehospitalization for an acute coronary syndrome at six months with a number needed to treat of approximately 29 patients.The subgroup analysis of this trial is particularly important and biologically plausible, as the presence of ST changes and level of cardiac biomarkers elevation indicate more significant myocardial ischemia or necrosis. Patients without ST changes comprised 62% of the study participants, while those with negative cardiac biomarkers made up 59%, and the study results should not be generalized to these subgroups.Another key consideration is the lack of detailed criteria for what was deemed ‘appropriate' revascularization. Only 60% of patients in the early invasive strategy group underwent revascularization, underscoring that not all patients with unstable angina or NSTEMI benefit from coronary angiography and that further risk stratification is necessary.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 2024;390:1481-1492Background: In patients with ST-elevation myocardial infarction (STEMI), opening the culprit artery improves outcomes. Nearly half of STEMI patients have disease in other coronary arteries. Whether revascularizing these non-culprit arteries improves outcomes remained uncertain. The PRAMI trial showed improvement in outcomes with complete revascularization but was relatively small, included 465 patients, and did not require the use of fractional flow reserve (FFR).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 FFR-Guidance for Complete Nonculprit Revascularization (FULL REVASC) trial sought to assess if FFR-guided completed revascularization improves outcomes compared to culprit-only percutaneous coronary intervention (PCI).The COMPLETE trial was not published by the time the FULL REVASC trial started enrolling patients.Patients: Eligible patients had STEMI and were undergoing PCI or had high risk NSETMI undergoing urgent PCI. High risk NSTEMI included patients with dynamic ST–T-wave changes, ongoing chest pain, acute heart failure, hemodynamic instability independent of electrocardiographic changes, or life-threatening ventricular arrhythmias.Eligible patients had to have multivessel coronary artery disease, defined as one or more lesions in a nonculprit artery with a diameter of ≥ 2.5 mm and a visually graded stenosis of 50 - 99%.Patients were excluded if they had previous CABG, left main disease or cardiogenic shock.Baseline characteristics: The trial randomized 1,542 patients – 778 randomized to culprit-only PCI and 764 randomized to complete revascularization. Patients were recruited from 32 centers in 7 countries.Approximately 91% of the patients had STEMI and 9% had high risk NSTEMI.The average age of patients was 65 years and 76% were men. Approximately 51% had hypertension, 16% had diabetes, 23% were on treatment for hyperlipidemia, 8% had prior myocardial infarction, and 35% were current smokers.The number of residual coronary arteries with stenosis of 50-99% was 1 in 72% of the patients and 2 or more in the rest.Procedures: Patients were randomly assigned in a 1:1 ratio to undergo culprit-only PCI or FFR-guide complete revascularization. The study was open label.Patients in the culprit-PCI only group did not receive further revascularization during the index hospitalization. Patients in the FFR-guided complete revascularization could receive further revascularization during the index procedure or during the index hospitalization. PCI of non-culprit lesion was recommended if FFR was 0.80 or less.Endpoints: The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The main secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularizationAnalysis was performed based on the intention-to-treat principle. The estimated sample size to achieve 80% with a two-sided alpha of 0.05 was 4,052 patients. This sample size would detect 0.75 risk ratio for the composite outcome of death or myocardial infarction at 1-year assuming 9.9% event rate in the culprit-only PCI. After the publication of the COMPLETE trial, the trial was stopped early due to ethical and feasibility concerns. Consequently, the original key secondary outcome (death from any cause, myocardial infarction, or unplanned revascularization) became the new primary outcome, and events after 1 year of follow-up were included in the primary analysis.Results: The trial was stopped after randomizing 38.1% of the original sample size. Among the patients assigned to the FFR-guided complete-revascularization arm, the procedure was followed in 95.9% of the patients, and among these patients, 17.9% underwent FFR-guided complete revascularization of non-culprit lesions during the primary PCI and the rest during the index hospitalization. Among the patients assigned to culprit-only arm, the assigned strategy was followed in 99.6% of the patients. The median follow-up time was 4.8 years.FFR was 0.8 or less in 392 (47.3%) of non-culprit vessels assessed, and PCI was performed in 369 (94.1%) of these vessels. In total, PCI was performed in 18.8% of the total non-culprit vessels. The average number of stents during the index hospitalization was 1 in the culprit-only PCI group and 2 in the complete revascularization group.The primary composite outcome was not significantly different between both treatment groups (19.0% with complete-revascularization vs 20.4% with culprit-only PCI, HR: 0.93, 95% CI: 0.74 - 1.17; p= 0.53). There were also no significant differences in composite endpoint of death from any cause or myocardial infarction (16.5% with complete revascularization vs 15.3% with culprit-only PCI) or unplanned revascularization (9.2% with complete revascularization vs 11.7% with culprit-only PCI).Stent thrombosis and stent restenosis were significantly more frequent in the complete revascularization arm (2.5% vs 0.9%, HR: 2.80, 95% CI: 1.18 – 6.67) and (4.2% vs 2.3%, HR: 1.84, 95% CI: 1.03 – 3.28), respectively.Baseline risk or coronary anatomy did not significantly affect subgroup interactions for the primary outcome.Conclusion: In patients with STEMI or high risk NSTEMI, FFR-guided complete revascularization compared to culprit-only PCI, did not improve the outcomes of death from any cause, myocardial infarction, or unplanned revascularization, over a median follow up time of 4.8 years. Complete revascularization resulted in more stent thrombosis and stent restenosis.The study lost some statistical power by stopping early, resulting in a final power of 74%. We disagree with the authors' decision to halt the trial prematurely based on the findings of the COMPLETE trial. COMPLETE was the first large trial to demonstrate a benefit in hard outcomes when revascularizing stable plaques, and its results warrant further confirmation. Furthermore, COMPLETE used different strategy as FFR was not required.Note to readers: Power measures the study's ability to avoid a Type II error (false negative) and it equals 1 - β with β being the probability of a Type II error. In other words, power represents the probability of correctly rejecting the null hypothesis (H₀) when the alternative hypothesis (H₁) is true. Most clinical trials aim for 80% or 90% power. For example, a study with 80% power has a 20% risk of failing to detect a real effect.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

THE LANCET 2011;377:1409-1420Background: When patients undergo coronary angiography, a hollow tube called a sheath is inserted into an artery. The primary function for the sheath is to provide a stable entry point into the artery, allowing for the safe navigation of instruments to the coronary arteries. Traditionally these sheaths were inserted into the femoral artery. One of the common complications associated with this approach is bleeding which is associated with worse outcomes. An alternative approach is inserting the sheath into the radial artery which is more superficial and more readily compressible compared to the femoral artery.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Small randomized trials suggested that a radial artery access is associated with less bleeding with possible reduction in death and myocardial infarctions but also a signal of increased percutaneous coronary intervention (PCI) failure.The RIVAL trial sought to assess if radial artery access is superior to femoral artery access in patients with acute coronary syndrome (ACS) undergoing coronary angiography.Patients: Patients had acute coronary syndrome and an invasive strategy was planned. Dual circulation of the hand, as assessed by an Allen's test, had to be intact.Patients were excluded if they had cardiogenic shock, severe peripheral vascular disease precluding a femoral approach, active bleeding or high bleeding risk, or prior coronary artery bypass grafting (CABG) with the use of more than one internal mammary artery graft.Baseline characteristics: The trial randomized 7,021 patients in 32 countries – 3,507 randomized to radial access and 3,514 to femoral access.The average age of patients was 62 years and 73% were men. Approximately 60% had hypertension, 21% had diabetes, 18% had prior myocardial infarction, 2% had prior CABG, 2% had peripheral vascular disease, and 31% were current smokers.The diagnosis at admission was unstable angina in 45% of the patients, NSTEMI in 27% and STEMI in 28%.The use of antiplatelet and anti-thrombotic drugs was not significantly different between both groups.Procedures: The RIVAL trial initially enrolled patients within the CURRENT-OASIS 7 trial which was a trial of antiplatelets therapy in ACS. After the conclusion of the CURRENT-OASIS 7 trial, RIVAL enrolled additional patients.Patients were assigned in a 1:1 ratio to undergo femoral or radial artery access. The use of anti-thrombotic regimen at the time of PCI as well as femoral artery closure devices was at the discretion of the treating physician.Endpoints: The primary outcome was a composite of all-cause death, myocardial infarction, stroke, or non-CABG related major bleeding, within 30 days. Secondary outcomes included the components of the primary outcome as well as major vascular access site complications and PCI procedural success.The components of the primary outcome were adjudicated by a central committee blinded to the treatment assignment. Major vascular access site complications and PCI procedural success were reported by the investigators.Analysis was performed based on the intention-to-treat principle. Due to low event rate, the sample size was increased from 4,000 to 7,000. This new sample size would provide 80% power to detect 25% relative risk reduction in the primary endpoint assuming 6% event rate in the femoral access arm.The study had six prespecified subgroup analysis: Age (< 75 vs older), sex, body mass index, STEMI vs no STEMI, operator's annual radial PCI volume and center's median operator's radial PCI volume.Results: Among the 7,021 randomized patients, 99.8% underwent coronary angiography. The rate of crossover was 7.6% in the radial group and 2.0% in the femoral group. Most of the crossover in the radial group was due to failure of the coronary angiogram using the radial approach. There was no significant difference in the number of PCI catheters used between both groups. Fluoroscopy time was higher in the radial group (7.8 minutes vs 6.5 minutes; p< 0.001).The primary composite outcome at 30-days was not significantly different between both groups (3.7% with radial vs 4.0% with femoral, HR: 0.92, 95% CI: 0.72 – 1.71; p= 0.50). All of the components of the primary outcome were not significantly different between both groups: 1.3% vs 1.5% for death, 1.7% vs 1.9% for myocardial infarction, 0.6% vs 0.4% for stroke, and 0.7% vs 0.9% for non-CABG related major bleeding.PCI procedural success was 95% in both groups. Major vascular complications were lower using the radial approach (1.4% vs 3.7%; p< 0.001). Major vascular complications were defined as pseudoaneurysms needing closure, large hematoma, arteriovenous fistula, or an ischemic limb needing surgery.There were no significant subgroup interactions based on age, sex, body mass index or operator's radial PCI volume. There was significant interaction based on STEMI vs no STEMI (p for interaction= 0.025) and center's radial PCI volume (p for interaction 0.021), such as patients with STEMI and patients in centers with the highest tertile for PCI volume had reduction in the primary outcome with radial access.Significantly more patients in the radial group said to prefer radial approach if they need a future coronary angiography (90.2% vs 50.7%; p< 0.001).Conclusion: In patients with acute coronary syndrome undergoing coronary angiography, a radial approach compared to femoral approach, did not improve the primary composite outcome of all-cause death, myocardial infarction, stroke, or non-CABG related major bleeding, at 30 days. A radial approach reduced major vascular complications with a number needed to treat of approximately 43 patients. A radial artery approach was more commonly preferred by patients for future coronary angiography.One of the limitations of this trial is that the outcome of major vascular complications is subject to bias as it was reported by the investigators rather than centrally adjudicated.Given that this trial compares two approaches with similar costs, the observed reduction in vascular complications justifies an increased adoption of the radial approach. The safety of the radial approach has likely improved over the years as centers and operators have gained more experience. Moreover, patients have shown a clear preference for the radial approach, which is an important win as well.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 2009;360:213-24Lancet 2015;386:1853-60Background: Fractional flow reserve (FFR) is a measure of the physiologic significance of a coronary stenosis that is defined as the ratio of maximal blood flow in a stenotic artery to normal maximal flow. It is measured during coronary angiography by calculating the ratio of distal coronary pressure measured with a coronary pressure guidewire to aortic pressure measured simultaneously with the guiding catheter. FFR in a normal coronary artery equals 1.0 whereas a value 90% and is similar to information obtained with stress imaging studies.For patients with multivessel coronary disease, it can be a challenge in the cath lab to differentiate between blockages causing ischemia and those that are not and this may be especially challenging when patients have not undergone stress imaging prior (e.g., patients presenting with acute coronary syndromes without ST segment elevation). The FAME trial sought to test the hypothesis that revascularization guided by FFR would be superior to revascularization guided by angiography alone in a broad cohort of patients with multivessel disease in whom revascularization with PCI was indicated.Patients: Patients with multivessel CAD of at least 50% of the vessel diameter in at least 2 of the 3 major epicardial coronary arteries in whom PCI was indicated. Patients with a STEMI could be included if the infarction occurred at least 5 days before PCI. Patients with a NSTEMI could be included earlier than 5 days. Patients who had undergone previous PCI could be included.Patients were excluded if they had left main coronary disease, previous CABG, cardiogenic shock, extremely tortuous or calcified coronary arteries, a life expectancy less than 2 years, a contraindication to the placement of drug-eluting stents, or if patients were pregnant.Baseline characteristics: Information is not provided on patients screened to enrolled. The average age of patients was 64.5 years and approximately three quarters were men. It is not clear from the main manuscript how many patients presented with acute MI's. It appears that approximately one third of patients presented with unstable angina and about half of these patients had dynamic ECG changes. More than half of patients in the trial had class 2 angina or below. Approximately 25% of patients had diabetes and over 60% had hypertension. The average EF was 57%.The mean number of lesions per patient was 2.8. About 40% of blockages were estimated to be in the 50-70% range, another 40% were in the 71-90% range, 15% were 91-99% narrowed and 3% were chronic total occlusions. The minimal luminal diameter was 1.0 mm, mean reference vessel diameter was 2.5 mm, mean lesion length was 12.5 mm and the SYNTAX score was 14.5.Procedures: Patients were randomized after they were found to have multivessel disease, meeting the study criteria, and were thought to require PCI. Patients assigned to angiography-guided PCI underwent stenting of all indicated lesions with drug-eluting stents. Those assigned to FFR-guided PCI underwent FFR in each diseased coronary artery and drug-eluting stents were placed in lesions with FFR that was /=50% in 2 of 3 major epicardial coronary arteries) and an indication for PCI, that FFR-guidance may reduce stent use and improve outcomes over short-term follow-up. However, more data is needed to confirm this result and to distinguish patient populations most likely to benefit based on clinical indication for PCI and complexity of coronary anatomy.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 2016;375:1242-1252Background: The first drug-eluting stent (DES) was approved by the FDA in 2003 following the publication of the RAVEL trial. Since then, newer generations of DES were developed and were tested in clinical trials. The majority of trials comparing DES to bare-metal stents (BMS) showed reduction in repeat revascularization with DES but no significant reduction in death or myocardial infarction. Following these publications, the use of DES grew rapidly and was used in more than two thirds of percutaneous coronary interventions (PCI) by 2010.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.These trials, however, were very selective, had short follow up time (TAXUS-IV followed patients for 9 months and SPRIT IV followed patients for 12 months), and had limited power to assess hard outcomes.The NORSTENT trial investigators sought to compare DES to BMS in a more pragmatic design and follow patients for longer time.Patients: All patients who were undergoing PCI in Norway were assessed for enrollment. Patients had stable angina or acute coronary syndrome. Lesions were in native coronary arteries or bypass grafts.Patients were excluded if they had prior coronary stents, bifurcating lesions requiring a two-stent technique or life expectancy less than 5 years due to a medical condition other than coronary artery disease. Patients were also excluded if they had contraindications to dual antiplatelets or were taking warfarin.Baseline characteristics: The trial randomized 9,013 patients – 4,504 randomized to receive a DES and 4,509 to receive a BMS.The average age of patients was 63 years and 75% were men. Approximately 42% had hypertension, 54% had hyperlipidemia, 10% had prior myocardial infarction, 7% had prior CABG, 12% had diabetes, and 35% were current smokers.The indication for PCI was stable angina in 29% of the patients, unstable angina in 12% and STEMI or NSTEMI in 58%.Procedures: The study was open-label but outcomes assessment was blinded. Patients were randomly assigned in a 1:1 ratio to receive DES or BMS. Patients could receive several stents as clinically indicated but can only receive the assigned stent type during the index procedure.In all patients, aspirin 75 mg daily was given indefinitely while clopidogrel 75 mg daily was given for 9 months.Follow up visits were done as clinically appropriate without specification from the study protocol. Similarly, no routine follow up coronary angiography was performed.Endpoints: The primary outcome was a composite of all-cause death or spontaneous myocardial infarction. Secondary outcomes included repeat revascularization, stent thrombosis, major bleeding and health status based on the Seattle Angina Questionnaire.Clinical outcomes were collected by linking each patient unique national identification number to the Norwegian national patient registry.Analysis was performed based on the intention-to-treat principle. The study planned to enroll 8,000 patients to be followed for a median of 5 years. Assuming the 5-year event rate of the primary outcome to be 17%, the study would provide 93% power to detect 3% absolute risk difference between the study groups (rate ratio: 1.18). Due to lower than expected mortality, the sample size was increased to 9,000 patientsResults: Among the 20,663 patients who were assessed for eligibility, 12,425 met inclusion criteria. Among patients who met inclusion criteria, 9,013 were randomized. Figure 1 in the manuscript provides details for excluding patients and for not randomizing patients who met eligibility criteria. The most common reason for exclusion was prior PCI.The number of stents implanted per patient was 1.7 and more than 98% received the assigned stent type. The median follow up time was 5 years.The primary composite outcome of all-cause death or nonfatal spontaneous myocardial infarction was not significantly different between both treatment arms (16.6% with DES vs 17.1% with BMS, HR: 0.98; 95% CI: 0.88 - 1.09; p= 0.66).For the secondary outcomes – Hospitalization for unstable angina was similar between treatment groups (5.2% vs. 5.7%; p= 0.21). Stent thrombosis was lower with DES (0.8% vs 1.2%; p= 0.05). Target-lesion revascularization was also lower with DES (5.3% vs 10.3%; p< 0.001). Bleeding Academic Research Consortium (BARC) 3, 4 or 5 was similar between groups (5.5% vs 5.6%; p= 0.88).There was no significant difference in health status based on the Seattle Angina Questionnaire.There were no significant subgroup interactions.Conclusion: In patients undergoing PCI, the use of DES did not reduce the composite endpoint of death or spontaneous myocardial infarction compared to BMS. Target-lesion revascularization was reduced with DES with a number needed to treat of 20 patients.The findings of this study align with the results of other trials comparing DES to BMS. We have reviewed several key trials and included links to additional studies in this field below. Overall, DES significantly reduce target-lesion revascularization without significant effect on all-cause mortality or myocardial infarction.An important consideration in this and other related trials is that both stent types were studied using similar durations of dual antiplatelet therapy (DAPT) following PCI. For patients with stable angina, BMS typically require only one month of DAPT, while DES often necessitate three to twelve months. Since shorter durations of DAPT are generally safer for patients, a trial comparing DES with three to twelve months of DAPT compared to BMS with one month of DAPT would be insightful.A final teaching point is that less than 50% of screened patients were ultimately enrolled in this pragmatic trial, which had minimal exclusion criteria. It's not uncommon for trials to enroll less than 5% of screened patients which limits their external validity.* Other trials of DES vs BMShttps://pubmed.ncbi.nlm.nih.gov/21080780/https://pubmed.ncbi.nlm.nih.gov/22951305/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

JACC Associate Editor Seng Chan You, MD, and author Hiroki Ueyama, MD discuss this study presented at AHA and published in JACC. NCDR study finds a steady decline in P2Y12 inhibitor pretreatment for NSTE-ACS in the US, but significant variability persists among operators, institutions, and regions. This practice was not associated with any benefits but was linked to a longer length of stay among those undergoing CABG, underscoring the importance of maintaining efforts to integrate evidence into clinical practice.

N Engl J Med 2022;386:128-137Background: Patients with three-vessel coronary artery disease have better outcomes when revascularization is performed using coronary artery bypass grafting (CABG) compared to percutaneous coronary intervention (PCI), as seen in the SYNTAX and FREEDOM trials. Fractional flow reserve (FFR) was not required and was not routinely performed in these trials.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 Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) 3 trial sought to compare the outcomes of FFR-guided PCI vs CABG in patients with three-vessel coronary artery disease.Patients: Eligible patients had three-vessel coronary artery disease defined as 50% or more stenosis, by visual estimation, in any of the three major coronary arteries or major branches. Lesions had to be amenable to revascularization by PCI and CABG as determined by the heart team.Major exclusion criteria were left main disease, cardiogenic shock, STEMI within 5 days, active NSTEMI with cardiac troponin still rising, left ventricular ejection fraction

King and I | S5 E5 | Should Elderly Patients Presented with NSTEMI Undergo Cath and PCI

Stay ahead with the newest cardiology research findings that could change your clinical practice! STUDY #1: First up, we explore new data on edoxaban dosage for older patients with atrial fibrillation. If we could give older patients a lower dose of edoxaban to reduce the risk of bleeding, will they still benefit from a lower risk for stroke?  Zimerman, A, Braunwald, E,  Steffel, J, et al. 2024. Dose reduction of edoxaban in patients 80 years and older with atrial fibrillation: Post hoc analysis of the ENGAGE AF-TIMI 48 randomized clinical trial. JAMA Cardiol. Published online. (https://doi.org/10.1001/jamacardio.2024.1793) STUDY #2: Next, we delve into the nuanced world of invasive versus noninvasive treatment of non-ST-segment elevation myocardial infarction (NSTEMI). You'll find out if mortality rates go up when we use a less invasive approach.  Kunadian, V, Mossop, H, Shields, C, et al. 2024. Invasive treatment strategy for older patients with myocardial infarction. N Engl J Med. Published online. (https://doi.org/10.1056/NEJMoa2407791) STUDY #3: Lastly, we break down the latest findings on chelation therapy in patients with stable coronary artery disease and diabetes. Tune it to see whether the latest data challenges your perspective on the efficacy of EDTA in reducing cardiovascular risks. Lamas, GA, Anstrom, KJ, Navas-Acien, A, et al. 2024. Edetate disodium-based chelation for patients with a previous myocardial infarction and diabetes: TACT2 randomized clinical trial. JAMA. Published online. (https://doi.org/10.1001/jama.2024.11463) Join us to uncover these critical insights, discussions, and more. Let's turn data into actionable wisdom and elevate your cardiology practice.  Learn more with Medmastery's courses: ECG Mastery Program (34 CME) Get a Basic or Pro account, or, get a Trial account. Show notes: Visit us at  https://www.medmastery.com/podcasts/cardiology-podcast.

Abdullah Al-Abcha, MD, social media editor of JACC: Cardiovascular Interventions, and Jun Jiang, MD, discuss a recently published original research paper on a study that aimed to evaluate the prognostic impact of coronary microvascular function in patients with NSTEMI, as determined by angio-IMR.

CardioNerds co-founder Dan Ambinder joins Dr. Lefan He, Dr. Sina Salehi Omran, and Dr. Neil Gupta from the University of Rochester Cardiovascular Disease Fellowship Program for a day sailing on Lake Ontario. Expert commentary is provided by Dr. Jeffrey Bruckel, and CV Fellowship Program Director Dr. Burr Hall shares insights on the University of Rochester fellowship. The episode audio was edited by CardioNerds intern Dr. Atefeh Ghorbanzadeh. They discuss the following case involving a patient with papillary muscle rupture. This is a 63-year-old man with hypertension, hyperlipidemia, and active tobacco smoking who presented with acute dyspnea. He was tachycardic but otherwise initially hemodynamically stable. The physical exam demonstrated warm extremities with no murmurs or peripheral edema. Chest X-ray revealed diffuse pulmonary edema, and the ECG showed sinus tachycardia with T-wave inversions in the inferior leads. A bedside echocardiogram revealed a flail anterior mitral valve leaflet. The patient was taken for cardiac catheterization that revealed nonobstructive mid-RCA atheroma with a distal RCA occlusion, which was felt to reflect embolic occlusion from recanalized plaque. PCI was not performed. Right heart catheterization then demonstrated a low cardiac index as well as elevated PCWP and PA pressures. An intra-aortic balloon pump was placed at that time. A TEE was performed soon after which showed the posteromedial papillary muscle was ruptured with flail segments of the anterior mitral leaflet as well as severe posteriorly directed mitral regurgitation. The patient ultimately underwent a successful tissue mitral valve replacement and CABG. US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! case Media Pearls - A Case of Papillary Muscle Rupture Most cases of papillary muscle rupture demonstrate only small areas of ischemia with preserved ventricular function, thus causing high shear force on the ischemic papillary muscle. The posteromedial papillary muscle has a single blood supply from the posterior descending artery, while the anterolateral papillary muscle has a dual blood supply from the LAD and the circumflex. Therefore, the posteromedial papillary muscle is more vulnerable to ischemia and, hence, rupture. A murmur may be absent in cases of papillary muscle rupture due to the rapid equalization of left atrial and left ventricular pressures caused by the acuteness of the severe MR. Papillary muscle rupture should always be on the differential for acute dyspnea when ACS is suspected. While mostly associated with STEMIs, mechanical complications of acute myocardial infarctions can also occur after NSTEMIs. Always auscultate patients carefully after a myocardial infarction! When evaluating patients with chest pain presenting with acute or rapidly progressive heart failure and a hypercontractile LVEF should raise suspicion for mechanical complications of MI. Once a papillary muscle rupture is diagnosed, cardiac surgery should be immediately contacted. Temporizing measures prior to surgery include positive pressure ventilation, IV nitroglycerin/nitroprusside, and temporary mechanical circulatory support. Notes - A Case of Papillary Muscle Rupture What is the clinical presentation of acute mitral regurgitation from papillary muscle rupture? Patients typically present 3-5 days after a transmural infarct. Roughly half of these patients present with pulmonary edema that may quickly progress to cardiogenic shock. Most cases are associated with STEMIs, but papillary muscle rupture is also possible with an NSTEMI.

MRAs in HF with renal dysfunction, coronary autoregulation, the hubris of US doctors, NSTEMI in older patients, survival after STEMI, and new leaders at JACC are discussed by John Mandrola, MD. This podcast is intended for healthcare professionals only. To read a partial transcript or to comment, visit: https://www.medscape.com/twic I Listener Feedback Combined analysis (Matsumoto) II Coronary artery autoregulation with increasing stenosis NEJM Paper https://www.nejm.org/doi/full/10.1056/NEJMc2402216 III RECOVER IV Trial Gregg Stone, MD Tweet https://x.com/GreggWStone/status/1803583552354742416 DANGER-Shock Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2312572 Impella Saves Lives in Cardiogenic Shock, but Patient Selection Key https://www.medscape.com/viewarticle/1000659 IV NSTEMI Elderly Main Paper Datamethods https://discourse.datamethods.org/t/random-vs-fixed-effects-meta-analysis/7361 O'Fee Paper https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2785560 V MI Survival Danish Paper https://doi.org/10.1016/j.jacc.2024.04.025 You may also like: The Bob Harrington Show with the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine, Robert A. Harrington, MD. https://www.medscape.com/author/bob-harrington Questions or feedback, please contact news@medscape.net

N Engl J Med 2015;372:2387-2397Background: Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, effectively lower low-density lipoprotein (LDL) and improve cardiovascular outcomes across different populations. High-intensity statins exhibit greater efficacy in lowering LDL and decreasing non-fatal cardiac events compared to moderate-intensity statins. Nonetheless, due to the residual risk of cardiac events, and concerns about the safety and tolerability of high intensity statins, there is a growing demand for newer therapeutic options.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.Ezetimibe acts on the Niemann–Pick C1–like 1 (NPC1L1) protein, inhibiting cholesterol absorption from the intestine. When combined with statins, ezetimibe further decreases LDL levels by an average of 23 to 24%.The IMPROVE-IT trial sought to test the hypothesis that adding ezetimibe to simvastatin is superior to simvastatin alone in reducing cardiovascular events in patients with recent acute coronary syndrome.Patients: Patients were enrolled if they had acute coronary syndrome (STEMI, NSTEMI or high-risk unstable angina) in the preceding 10 days, and were at least 50 years old. LDL levels within 24 hours of the acute coronary syndrome (ACS) had to be at least 50 mg/dL but less than or equal to 125 mg/dL in lipid-therapy naïve patients or less than or equal to 100 mg/dL in patients receiving lipid lowering therapy. Patients were excluded if they had hemodynamic or electrical instability following the ACS event, planned CABG, active liver disease, creatinine clearance< 30 ml/min, or they had chronic lipid lowering therapy of simvastatin> 40mg, atorvastatin 40mg or more, any dose of rosuvastatin, or any ezetimibe/simvastatin combination.Baseline characteristics: The average age of patients was 64 years with 76% being men. The average weight was 83 kg. About 27% had diabetes, 61% had hypertension, 21% had prior myocardial infarction, 4% had congestive heart failure and 33% were current smokers. The median creatinine clearance was 85 ml/ min. The index event was STEMI in 29% of the patients, NSTEMI in 47% and unstable angina in the rest. Coronary angiogram was performed in 88% of the patients and percutaneous coronary intervention was performed in 70%. The mean LDL was 94 mg/dL and was similar in both groups.Procedures: Patients were randomized 1:1 in a double blinded fashion to receive simvastatin 40mg daily plus ezetimibe 10mg daily or simvastatin 40mg daily plus placebo. Patients had follow-up visits at 30 days, 4 months, and every 4 months thereafter.In both study groups, if LDL level was higher than 79 mg/dL on two consecutive measurements, the simvastatin dose was increased to 80 mg per day. This practice continued until June 2011, approximately one year after the study's randomization concluded, when the Food and Drug Administration advised limiting new prescriptions of simvastatin 80 mg daily. If LDL levels were higher than 100 mg/dL on the new regimen, the study drug could be discontinued, and more potent therapy could be initiated. Patients were followed for at least 2.5 years and for up to 7 years.Endpoints: The primary efficacy end point was a composite endpoint of death from cardiovascular disease, a major coronary event (defined as nonfatal myocardial infarction, unstable angina requiring hospital admission, or coronary revascularization occurring at least 30 days after randomization), or nonfatal stroke. The trial also reported death from any cause as part of one of the secondary composite endpoints. Safety variables included liver enzymes and creatine kinase levels, myopathy or rhabdomyolysis, gallbladder-related adverse events or cancer.Statistical analysis was performed based on the intention-to-treat principle. To achieve 90% power for detecting 9.375% lower relative risk for the primary end point with simvastatin–ezetimibe combination compared to simvastatin alone, an estimated sample size of 18,000 patients and 5,250 primary events was required.Results: The trial randomized 18,144 patients in 39 countries; 9067 randomized to the simvastatin–ezetimibe combination and 9077 to the simvastatin monotherapy group.The simvastatin–ezetimibe combination led to greater reduction in LDL. At 1 year, the mean LDL was 53 mg/dL in the simvastatin–ezetimibe combination group and 70 mg/dL in the simvastatin monotherapy group. The simvastatin dose was increased to 80mg per day in 6% of the patients in the simvastatin–ezetimibe group and 27% in the simvastatin monotherapy group.The use of simvastatin–ezetimibe led to greater reduction in the primary endpoint compared simvastatin monotherapy (32.7% vs 34.7%, HR: 0.94; 95% CI: 0.89 - 0.99; p= 0.016). This reduction in the composite primary endpoint was primarily driven by reduction in non-fatal myocardial infarction (12.8% vs 14.4%) as well as ischemic stroke (3.4% vs 4.1%). There was no significant difference in death from any cause (15.4% vs 15.3%) or death from cardiovascular causes (6.9% vs 6.8%).The benefits of simvastatin–ezetimibe were more pronounced in patients who were 75 years or older (39.0% vs 47.6%, HR 0.80, 95% CI: 0.70 - 0.90; p for interaction= 0.005) and in patients with diabetes (40.0% vs 45.5%, HR: 0.86, 95% CI: 0.78 - 0.94; p for interaction= 0.023).No significant differences in safety endpoints were observed between both groups. Elevation of liver enzymes 3 times or more the upper limited of normal occurred in 2.5% of the patients in the simvastatin–ezetimibe combination group and 2.3% in the simvastatin monotherapy group.Conclusion: In patients with recent acute coronary syndrome, the combination of simvastatin–ezetimibe as compared to simvastatin monotherapy improved the primary composite outcome of death from cardiovascular disease, major coronary events, or nonfatal stroke. This reduction was modest, about 6% relative reduction, and was primarily driven by reduction in non-fatal myocardial infarctions and ischemic strokes. The trial results supports the hypothesis that lower LDL levels improves outcomes regardless of how it's achieved. The trial has good interval validity but the external validity is limited in the current era because simvastatin is infrequently used nowadays with atorvastatin and rosuvastatin being the preferred agents. Patients taking atorvastatin 40mg or more and patients taken any dose of rosuvastatin at baseline were excluded from the trial. Furthermore, it's unclear why the trial did not permit the inclusion of patients whose LDL exceeded certain limits as only patients with mild elevation in LDL at baseline were permitted to be enrolled.This trial does not answer the question most physicians may encounter in their practice: What's the benefit of adding ezetimibe to high-intensity statins or prescribing it to patients with moderate or high elevation in LDL levels?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

N Engl J Med 2019;381:1524-1534Background Dual antiplatelet therapy after percutaneous coronary intervention had become a standard of care. Both prasugrel and ticagrelor had been shown to provide more rapid and consistent platelet inhibition than clopidogrel. Randomized controlled trials had shown both drugs were superior to clopidogrel in patients with acute coronary syndromes. 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 two drugs have different loading strategies in patients who have acute coronary syndromes without ST-segment elevation. In these patients, ticagrelor is usually administered as pretreatment before diagnostic angiography, but prasugrel is administered only after the coronary anatomy has been assessed by means of diagnostic angiography since no advantage has been observed when prasugrel is used as pretreatment.Before ISAR-REACT 5, there had been no direct comparisons of the two antiplatelet drugs. ISAR-REACT 5 was an investigator-initiated multicenter, non-industry funded RCT to compare the efficacy and safety of the two treatments in patients with acute coronary syndrome. Patients The trial enrolled 4013 patients from 23 centers. Patients were eligible with either STEMI, NSTEMI or unstable angina for which intervention was planned. Exclusion criteria included intolerance of either drugs, history of stroke or intracranial bleeding or any condition that increased the risk of bleeding. Patients could not be on concomitant oral or i.v. therapy with drugs affecting CYP3A4 system. Baseline Characteristics There were 2012 patients assigned to ticagrelor and 2006 patients assigned to prasugrel. The suspected diagnosis at admission was STEMI in 41%, NSTEMI in 46%, and unstable angina in 13% of the patients. The average age was 64 years. Female sex was 24%. Average systolic blood pressure and heart rate was 144 mmHg and 77 bpm. All factors were well balanced. Trial Procedures Therapy with ticagrelor was started at a loading dose of 180 mg and continued at a maintenance dose of 90 mg twice daily. Patients who were assigned to ticagrelor received the loading dose as soon as possible after randomization. Therapy with prasugrel was started at a loading dose of 60 mg and continued at a maintenance dose of 10 mg once per day. A reduced maintenance dose of 5 mg daily was recommended in patients who were 75 years of age or older and in those who had a body weight of less than 60 kg. Prasugrel therapy turned on presentation. STEMI patients were given prasugrel as soon as possible after randomization. In those without STEMI, the loading dose was delayed until knowledge of the coronary anatomy. Prasugrel loading was given before crossing the lesion. In patients with a coronary angiography–confirmed acute coronary syndrome who were not considered to be candidates for PCI but who were considered to be candidates for conservative therapy, dual antiplatelet therapy (aspirin and the randomly assigned trial medication) was recommended. About 83% of patients received PCI, 2% CABG and 13-14% were managed conservatively. Clinical follow-up was scheduled at 30 days, 6 and 12 months.Endpoints The primary end point was a composite of death, MI, or stroke at 1 year after randomization. Secondary end points included the safety end point, which was the incidence of bleeding at 1 year (type 3, 4, or 5 on the Bleeding Academic Research Consortium [BARC] scale, which ranges from 0 to 5, with higher values indicating more severe bleeding), the incidence of the individual components of the primary end point at 1 year, and the incidence of definite or probable stent thrombosis at 1 year.The sample-size calculation assumed a primary endpoint would occur in 10% in the ticagrelor group vs 12.9% in the prasugrel group. This led to an estimate of 1900 patients in each group and 80% power to detect a relative risk reduction of 22% in the ticagrelor group. All analyses, including the analysis of the primary end point, were performed according to the intention-to-treat principle Only the safety end point was analyzed in a modified intention-to-treat population, which included all patients who received at least one dose of the randomly assigned trial drug and were assessed for bleeding events up to 7 days after discontinuation of the trial drug.Results At discharge, 81% of patients in both groups received the randomly assigned trial drug. Slightly more patients in the ticagrelor group stopped taking the study drug by one year (15.2 vs 12.5%). One-year follow-up was complete in all but 90 patients (41 patients in the ticagrelor group and 49 patients in the prasugrel group).A primary end-point event (death, MI, stroke) occurred in 184 of 2012 patients (9.1%) in the ticagrelor group and 137 of 2006 patients (6.8%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P=0.006). The composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 161 of 2012 patients (8.1%) in the ticagrelor group and 124 of 2006 patients (6.3%) in the prasugrel group (hazard ratio, 1.32; 95% CI, 1.04 to 1.66).The rates of death, stroke and stent thrombosis did not statistically differ in the two groups. But the risk of MI was 63% higher in the ticagrelor group (4.8% vs 3.0%; HR 1.63; 95% CI, 1.18 to 2.25).Major bleeding was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P=0.46).No heterogenous treatment effects were obvious from the subgroup analyses. Discussion For patients with acute coronary syndrome who were considered for intervention, prasugrel was superior to ticagrelor for the reduction of the primary endpoint. The effect size was large (ticagrelor 36% worse compared to prasugrel), and this was statistically robust. The reduction was obtained without an increase in bleeding. The trialists noted that this was not simply a comparison of drugs, but a comparison of treatment strategies. Authors had assumed that pre-treatment of ticagrelor would be superior. But this trial showed that a prasugrel-based strategy with deferred loading (after knowing the coronary anatomy) was superior. The primary endpoint finding was bolstered by the composite of cardiovascular death, MI and stroke also being 32% higher in the ticagrelor arm. This was an investigator-initiated non-industry funded study with an event rate in the ticagrelor arm similar to expected findings. We find this compelling evidence for the superiority of prasugrel in this patient population. 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

How many EKGs does an emergency doctor interpret per shift? How many seconds of undivided attention can be devoted to those readings? Let's go over 7 key findings you can't miss for occlusive myocardial infarctions, with EMRA*Cast host Will Smith, MD, and emergency physician Domenico Mastandrea, DO, of Nuvance Health.

CardioNerds, Dr. Richard Ferraro and Dr. Dan ambinder join Dr. Li Pang, Dr. Emily Hendricks, and Dr. Bei Jiang from West Virginia University to discuss the following case that features apical obliteration with biventricular thrombus. Dr. Christopher Bianco provides the Expert CardioNerd Perspectives & Review (E-CPR) for this episode. Audio editing by CardioNerds Academy Intern, student doctor Tina Reddy. A 37-year-old Caucasian man with a history of tobacco smoking and hypertension who presented with chest pain and elevated troponin was admitted for non-ST elevation myocardial infarction (NSTEMI). Ischemic evaluation with an invasive coronary angiogram was negative. He was treated as NSTEMI and scheduled for outpatient cardiac MRI (CMR). The patient came back 2 months later with right arm weakness and confusion and was found to have an embolic stroke. Labs showed positive troponin with a flat trend and hypereosinophilia. Transthoracic echocardiogram (TTE) showed obliteration of LV and RV apex with thrombus and reduced LV systolic function. CMR was consistent with myocarditis with biventricular thrombus. The patient was started on corticosteroids and warfarin. Hypereosinophilia workup was positive for PDGFRA alpha rearrangement. He was diagnosed with primary hypereosinophila syndrome. Imatinib was initiated. The patient was followed up with the hematology clinic, achieved a complete hematologic response with normalized cell count, and remained free from any cardiovascular event at the 8-month follow-up. US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Case Media Pearls - Apical Obliteration with Biventricular Thrombus Cardiac MRI is a valuable test for patients presenting with myocardial infarction with non-obstructive coronary arteries (MINOCA). Obliterated apex with apical thrombus on TTE with hypereosinophilia should raise high suspicion for eosinophilic myocarditis. Initiation of corticosteroids is the first-line treatment for eosinophilic myocarditis, which is associated with lower mortality in patients with myocarditis. For other potential complications, such as heart failure, intracardiac thrombus, arrhythmia, and pericardial effusion, the standard of care for each disorder is recommended. Hypereosinophilia can be seen in parasitic infections, vasculitis, asthma, allergy, hematological malignancies, and as a primary disorder. Show Notes - Apical Obliteration with Biventricular Thrombus What is the differential diagnosis for patients with elevated troponin and nonobstructive CAD? The occurrence of acute myocardial infarction (AMI) without significant CAD was reported 80 years ago. However, the term MINOCA (myocardial infarction with non-obstructive coronary arteries) has only been used recently to describe these patients. It involves ischemic and nonischemic etiologies. First, overlooked ischemic etiologies need to be ruled out by reconciling the angiogram images such as spontaneous coronary artery dissection (SCAD) and plaque disruption. Intracoronary imaging, such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT), may be applied to evaluate for SCAD and subtypes of plaque disruption when indicated.  The investigation continues with nonischemic causes such as stress cardiomyopathy, myocarditis, pulmonary embolism, demand ischemia from sepsis, anemia, chest trauma, heart failure exacerbation, arrhythmia, and stroke. The diagnosis of MINOCA is established when it fulfills the following criteria: First, it is AMI by the Fourth Universal Definition; Second, less than 50% of stenotic lesion on angiogram; Third, there is no alternate diagnosis.

N Engl J Med 2012;366:9-19Background Following an acute coronary syndrome, individuals have a substantially elevated risk of recurrent events, compared to a similar individual who did not experience ACS, despite the use of appropriate risk reducing therapies. This is termed “residual risk” and the concept has been mentioned in prior reviews. The quest to lower residual risk continues to be a major driver of new products and therapeutic concepts in cardiovascular medicine.Rivaroxaban is an oral anticoagulant that directly and selectively inhibits factor Xa. Factor Xa initiates the final common pathway of the coagulation cascade resulting in the formation of thrombin. Thrombin promotes platelet aggregation. At the time the trial was undertaken, both aspirin and thienopyridines were established agents that worked via different mechanisms, downstream of thrombin formation, to stop platelets from sticking together. Could the addition of an agent that inhibits thrombin formation, upstream of platelet activation and aggregation, reduce risk further without causing a prohibitive increase in bleeding risk?A meta-analysis of small trials involving the use of warfarin, in addition to aspirin, suggested that warfarin, an indirect inhibitor of thrombin, could improve cardiovascular outcomes. And a phase 2 dose finding trial with rivaroxaban provided further support. Thus, the ATLAS ACS-TIMI 51 trial sought to test the hypothesis that adding rivaroxaban to standard therapies, at 2.5 or 5 mg twice daily, would reduce cardiovascular events compared to 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 Adults who had presented with an acute coronary syndrome (STEMI, NSTEMI or unstable angina). Patients under 55 years of age had to have either diabetes or a history of a previous MI. Patients were excluded if they had a platelet count

N Engl J Med 2010;363:930-942Background By 2010, dual antiplatelet therapy had been established as beneficial during and after percutaneous coronary intervention for acute coronary syndromes. Optimal dosing however remained unknown. This included the best loading dose of clopidogrel and optimal dose of aspirin.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 Clopidogrel and Aspirin Optimal Dose Usage to Reduce Recurrent Events−Seventh Organization to Assess Strategies in Ischemic Syndromes (CURRENT–OASIS 7) trial was designed to determine whether a doubling of the loading and initial maintenance doses of clopidogrel is superior to the standard-dose regimen and whether higher-dose aspirin (300 to 325 mg daily) is superior to lower-dose aspirin (75 to 100 mg daily) in patients with acute coronary syndromes referred for an early invasive strategy.Patients Adult patients who presented with a non-ST-segment elevation acute coronary syndrome (ACS) or an ST-segment elevation myocardial infarction. Patients had to have had coronary angiography with a plan to perform PCI within 72 hours. Major exclusion criteria were an increased risk of bleeding or active bleeding and a known allergy to clopidogrel or aspirin. Baseline Characteristics Nearly all patients had angiography. About 68% had PCI and 32% did not have PCI due to lack of significant (≤70%) stenosis. About a quarter of patients had coronary-artery bypass surgery. The average age of patients was 61 years; 27% female sex, and 70% had a diagnosis of unstable angina or NSTEMI. The median time to randomization in patients with unstable angina/NSTEMI was 3.4 days vs 0.6 days in patients with STEMI. About 60% of patients were white, and 22% were Asian. The co-existing cardiac risk factors, such as smoking, hypertension, diabetes and previous MI were similar in all the trial arms, and typical of most trials at the time.Procedures The CURRENT-OASIS 7 trial had 2x2 factorial design. First, comparing in a double-blind fashion, a double dose vs standard dose clopidogrel regimen. In the second component, patients were randomly assigned in an open-labeled fashion to higher- or lower-dose aspirin.Immediately after randomization and before coronary angiography, patients randomly assigned to double-dose clopidogrel received a loading dose of 600 mg on day 1, followed by 150 mg once daily on days 2 through 7. Patients assigned to standard-dose clopidogrel received a 300-mg loading dose on day 1 before angiography, followed by 75 mg once daily on days 2 through 7. On days 8 through 30, both the double-dose and standard-dose groups received 75 mg of clopidogrel once daily.Patients randomly assigned to lower-dose aspirin received 75 to 100 mg daily on days 2 through 30, and those randomly assigned to higher-dose aspirin received 300 to 325 mg daily on days 2 through 30. An initial loading dose of aspirin 300 mg was used in both arms on day 1. Other therapies, such as anti-thrombotics were left to the discretion of the treating doctors. Endpoints The primary endpoint was cardiovascular death, myocardial infarction, or stroke at 30 days. The sample-size calculation estimated an event rate of 11% at 30 days with standard-dose clopidogrel or lower-dose aspirin. That would have led to 14,000 patients to have 90% power to detect a 16% reduction in the primary endpoint. Lower-than expected event rates required an increase in sample size to 25,000 patients. This allowed for an 80% power to detect a 16% reduction in the primary endpoint.Results  A primary outcome event occurred in 4.2% of patients in the double-dose clopidogrel group at 30 days, as compared with 4.4% in the standard-dose group (hazard ratio, 0.94, 95% confidence interval [CI], 0.83 to 1.06; P=0.30). The rate of death from any cause did not differ significantly between the double-dose and standard-dose groups (2.3% and 2.4%, respectively; hazard ratio with the double dose, 0.96; 95% CI, 0.82 to 1.13; P=0.61). Major bleeding occurred more often in the double-dose arm (2.5 vs 2.0% HR 1.24; 95% CI 1.05-1.46).For the aspirin comparison, the rate of primary outcome events did not differ: 4.2% in the higher-dose arm vs 4.4% in the lower-dose arm. Death from any cause was not statistically different in either arm. Major bleeding rates were also similar in the two aspirin arms (2.3% in both arms).The authors described a “nominally significant” interaction between clopidogrel dose and aspirin dose for the primary outcome. Among patients assigned to higher-dose aspirin, the primary outcome occurred in 3.8% of patients in the double-dose clopidogrel group, as compared with 4.6% of patients in the standard-dose clopidogrel group (hazard ratio, 0.82; 95% CI, 0.69 to 0.98; P=0.03). But in the lower dose aspirin group, there were no significant differences in the primary outcome between double-dose and standard-dose clopidogrel (4.5% vs 4.2% HR 1.07 95% CI 0.90-1.26, respectively). The p-value for the interaction here was 0.04. Subgroup analyses showed generally consistent results. One possible heterogenous treatment effect in the double- vs standard-dose clopidogrel comparison turned on whether the patient had PCI or did not have PCI. In the 68% (≈17,000) of patients who had PCI, double dose clopidogrel reduced the primary outcome by 15% (3.9% vs 4.5%) vs increasing it by 14% in the no PCI group (4.9% vs 4.3%). The p-value for interaction was 0.03. There were no indications of heterogenous treatment effects depending on aspirin.Conclusions In patients with ACS, double dose clopidogrel or aspirin compared to standard dose did not significantly reduce the composite endpoint of cardiovascular death, MI or stroke. Double dose clopidogrel did increase major bleeding with a NNH of approximately 200 patients. Treatment effect heterogeneity, favoring the double dose clopidogrel strategy, was suggested for patients undergoing PCI.This trial serves as a good example of the limitations of surrogate endpoints in predicting hard outcomes. Previous studies had demonstrated that higher doses of clopidogrel led to faster and more substantial platelets inhibition. The observed increase in bleeding events with double-dose clopidogrel supported these findings. Nonetheless, it did not correspond to better ischemic outcomes.As for the dose of aspirin, there was no added benefit (or increase in bleeding) with higher dose aspirin beyond 75-100 mg. 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

Note to readers: Since going live with Cardiology Trials Substack in January of 2024 we have been exclusively covering trials that we have categorized as belonging to the major subject heading “Acute Coronary Syndrome” belonging to the subsection “Medicines”. Our indexing scheme was described in one of our original posts and we encourage our audience to read it if you have not already. This is pertinent because the next several trials being presented may seem to come out of the blue but we assure you there is a method.N Engl J Med 2007;357:2011-15.Background Up to now we have presented trials involving major foundational medical therapies for acute coronary syndrome which include aspirin, thrombolytic agents and anticoagulation, but not those involving percutaneous coronary intervention (PCI) as they are reserved for another section. But, by the turn of the 21st century, PCI had become the dominant up-front strategy for revascularization in many countries around the world. Clinical trials demonstrated it improved outcomes, the main one being re-infarction, compared to thrombolysis in patients with STEMIs, and there was an evolving evidence for it in non-ST-segment elevation acute coronary syndrome (STEACS) as well, where thrombolysis had not demonstrated any significant benefits.As PCI became dominant, antithrombotic strategies for optimizing outcomes following PCI evolved along with it. These early trials generally involved a mixture of patient phenotypes (acute vs elective PCI) and were relatively small and of limited quality by comparison to many of the seminal trials presented thus far. Instead of presenting each of these smaller studies, we direct readers to a narrative review that nicely describes the evolution of dual-antiplatelet therapy for PCI and other indications.Briefly: dual-antiplatelet therapy with aspirin and ticlopidine, an antiplatelet agent belonging to the drug class of thienopyridines, which inhibits platelet aggregation induced by ADP, was found superior to aspirin alone or aspirin plus anticoagulation when PCI was performed; however, there were concerns about its safety. Clopidogrel was developed after ticlopidine; it had a similar mechanism of action but less safety concerns and could be given as a loading dose to produce more rapid effects. Despite limited evidence from clinical trials comparing it head-to-head with ticlopidine it became the dominant thienopyridine agent on the market and still has a prominent role in the management of cardiovascular diseases today.Following PCI and dual-antiplatelet therapy with aspirin and clopidogrel, patients continue to have an elevated risk of coronary events, in general, and in-stent related coronary events, in particular. Some of this risk has been attributed to limitations of clopidogrel itself. Clopidogrel has modest antiplatelet effects (compared to other thienopyridines) with substantial interpatient variability due to genetic polymorphisms that impact clopidogrel metabolism and antiplatelet efficacy. Clopidogrel also has a delayed onset of action, which is especially relevant regarding its ability to protect against the dreaded adverse event of early in-stent thrombosis.Prasugrel is a thienopyridine—developed after clopidogrel—that inhibits platelet aggregation more rapidly, consistently and to a greater extent. The Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction (TRITON–TIMI) 38 trial sought to test the hypothesis that prasugrel would reduce major cardiovascular events compared to clopidogrel in patients with acute coronary syndrome undergoing PCI.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 had either moderate-to-high risk unstable angina (UA) or NSTEMI or STEMI. UA and NSTEMI were defined by ischemic symptoms lasting 10 minutes or more and occurring within 72 hours before randomization, a TIMI risk score of 3 or more, and either ST-segment deviation of 1 mm or more or elevated levels of a cardiac biomarker of necrosis. STEMI was traditionally defined. Key exclusion criteria included an increased risk of bleeding, anemia, thrombocytopenia, a history of pathologic intracranial findings, or the use of any thienopyridine within 5 days before enrollment.Baseline characteristics The median age of patients was 61 years with 13% being ≥75 years and 74% were men; over 90% were white. The index event was UA or NSTEMI in 74% and STEMI in 26%.  PCI was performed in 99% of patients and split evenly between those receiving bare metal or drug eluting stent(s).  18% of patients had a prior MI, 23% had diabetes, 64% had hypertension and 38% were tobacco users. Only 11% of patients had CKD defined as a creatinine clearance ≤60 ml/min.Procedures A loading dose of prasugrel 60 mg or clopidogrel 300 mg was given in a double blind manner anytime between randomization up to 1 hour after leaving the catheterization laboratory. In order to be randomized, the plan for PCI had to be known. This could occur before going to the cath lab for planned PCI, if the anatomy was already known or occur in the cath lab during the case where anatomy was determined and PCI was performed. If PCI was planned, patients were eligible to undergo pretreatment with the study drug for up to 24 hours prior to PCI.Treating physicians determined the vessels treated, devices used, and adjunctive medication administered to support PCI. After PCI, patients received maintenance doses of either prasugrel 10 mg daily or clopidogrel 75 mg daily. Use of aspirin at a dose of 75 to 162 mg daily was recommended. Study visits were conducted at hospital discharge, 30 days, 90 days, and 3-month intervals thereafter, for a total of 6 to 15 months.Endpoints The primary efficacy endpoint was a composite of cardiovascular death, nonfatal MI or stroke during the follow up period. A prespecified “landmark” analysis was undertaken to compare the primary endpoint event rate up to 3 days following randomization and from day 3 to the end of the study. The sample size calculation was event-driven and it was determined that 875 primary endpoint events would provide 90% power to detect a relative risk reduction of 20%. A prespecified analysis performed after 650 events revealed a lower than anticipated event rate and the investigators increased the sample size accordingly.Results A total of 13,608 patients (10,074 with UA or NSTEMI and 3534 with STEMI), from 707 sites in 30 countries were enrolled. There were 6,813 patients assigned to the prasugrel group and 6,795 assigned to clopidogrel. The median duration of therapy was 14.5 months. Prasugrel significantly reduced the primary composite endpoint compared to clopidogrel (9.9% vs 12.1%; HR 0.81; 95% CI 0.73-0.90; P

It's only been a year and Maddie's addicted to mobile games. Has it been a while? It's been a long time. 53yo M w PMH of HTN, HLD, DM2 p/w NSTEMI w CP. Check out Binging with Bbirchtats on YouTube: https://www.youtube.com/watch?v=i6djKQIviwk Ride on the magic council! I went to the school to get the D. Dimothy? Doug Dimmidome? Drubder? YOU DON'T HAVE PARENTS! This anime is trash and I'm Oscar THE FUCKING GROUCH. This dying thing is sick... Triggering all chemists. Say hello to GUMBO, THE DESTROYER OF WORLDS. Has Jim been uploading to YouTube for us?? We know our FBI guy is at least named ..... Eddd.... Wurddd? He knows at least 3 of the 5 guys! The milkman, the paper boy, THE EVENING TV. Gariel and Angelo, the cats who love you.   If you'd like to request us to cover YOUR favorite anime on My Favorite Anime, then donate on Ko-fi or Patreon https://ko-fi.com/myfavoriteanime https://www.patreon.com/mfanime Merch is back up (with some exclusive patreon merch soon): https://animate-station.creator-spring.com/listing/tanks-are-for-girls-my-favor Links to the podcast: https://open.spotify.com/show/0AV1raD6J16xjX5sVTuqNR?si=s1174woBQMSAlEAdZZqKgQ https://pca.st/BA5s https://podcasts.apple.com/us/podcast/my-favorite-anime/id1448147787

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

N Engl J Med 2001;345:494-502.Background The established medical treatments for acute coronary syndrome reviewed so far include aspirin and thrombolytics along with a smaller role for short-term anticoagulation. Angiotensin converting enzymes inhibitors and, to a lesser extent, beta blockers were also found to reduce recurrent ischemic events and death as well as heart failure and ventricular remodeling. The EPHESUS trial, which studied Eplerenone in this patient population was not published until several years later.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Despite the benefits of the above therapies, patients who experienced an ACS event were still at a substantially higher risk for experiencing recurrent events compared to patients who never experienced an ACS event. Significant interest remained in finding additional agents to reduce “residual risk” (i.e., the risk of recurrent events that is left over after initiating effective therapies). Imagine a heart attack survivor has a 20% risk of experiencing death, non-fatal MI or heart failure over the next 5 years. Now imagine that all known effective therapies cumulatively reduce that risk by 30% (a 6% absolute reduction in risk); the residual risk for events over 5 years would still be 14%, which is still high, and significantly higher than patients who never experienced an ACS event (e.g., primary prevention patients).Thienopyridine derivatives, including clopidogrel, are antiplatelet agents with a different mechanism of action than aspirin. Up to this point in time they demonstrated efficacy in patients who had received a coronary stent for reducing myocardial infarction compared to either aspirin alone or warfarin. The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial sought to test the hypothesis that 3 to 12 months of clopidogrel plus aspirin versus aspirin alone would reduce the rate of cardiovascular events (a composite endpoint) compared to aspirin alone in patients with ACS and no ST-segment elevation.Patients Patients were eligible if they had been hospitalized within 24 hours after the onset of symptoms, who had either ECG changes or an elevation in cardiac enzymes at entry, and did not have ST-segment elevation. Exclusion criteria included a contraindication to antithrombotic or antiplatelet therapy, high bleeding risk or severe heart failure, those who were taking oral anticoagulants, and those who had undergone coronary revascularization in the previous 3 months or had received intravenous glycoprotein IIb/IIIa receptor inhibitors in the previous 3 days.Baseline characteristics No information in the main manuscript is provided on the ratio of patients eligible to those enrolled, which limits our ability to make inferences about external validity. The average age of participants was 64 years of age and nearly 40% were woman, which is historically higher than the trials reviewed up to this point. The average time from pain onset to randomization was 14 hours. The diagnoses at study entry were unstable angina in 75% and MI in 25%. Many patients in the trial has a history of MI (32%) or revascularization (18%) in the past and the majority were either current or former smokers (61%). Most patients (94%) had some ECG abnormality; the most common being ST depression (42%) and T-wave inversion (36%).Procedures Immediately following randomization patients were administered a 300 mg loading dose of clopidogrel or matching placebo followed by 75 mg per day of clopidogrel or matching placebo for 3 to 12 months (the mean duration of treatment was 9 months). Aspirin was started or continued simultaneously with the study drug or placebo. Follow-up assessments occurred at discharge, at 1 and 3 months, and then every 3 months until the end of the study (12 months).Endpoints The first primary endpoint was the composite of death from cardiovascular causes (death for which there was no clearly documented nonvascular cause), nonfatal MI (which required at least 2 of 3 findings: ischemic chest pain, elevation of cardiac markers or ECG changes consistent with MI) or stroke (new focal neurological deficit of vascular origin lasting >24 hr and was subdivided into intracranial hemorrhage, ischemia, or uncertain cause) at 12 months. The second primary endpoint was the composite of the first primary endpoint or refractory ischemia. Secondary outcomes included severe ischemia, heart failure, and the need for revascularization. Safety related outcomes included life-threatening, major bleeding (requiring transfusion of ≥2 units of blood) or all other bleeding.The study was initially designed to include 9000 patients, with an anticipated primary event rate of 12-14% in the placebo group; however, because the event rate was lower than anticipated, the size of the study was increased as the trial was ongoing, with an adjusted rate of 10% in the placebo group. A final sample size of 12,500 patients was based on an anticipated 17% risk reduction for the primary composite endpoint with 90% power and a two-sided alpha level of 0.045.Results 12,562 patients were included in the final analysis; 6,303 in the placebo group and 6,259 in the clopidogrel group. During the initial hospital stay, 21% of patients in the clopidogrel group and 23% of patients in the placebo group underwent revascularization. At 1-year clopidogrel significantly reduced the occurrence of the first primary composite endpoint (RR 0.80; 9.3% vs 11.4%; 95% CI 0.72-0.90) and second primary composite endpoint (RR 0.86; 16.5% vs 18.8%; 95% CI 0.79-0.94). These differences were driven primarily by reducing nonfatal MI (RR 0.77; 5.2% vs 6.7%; 95% CI 0.0.67-0.89). There were no significant differences in death from cardiovascular or non-cardiovascular causes, stroke or refractory ischemia.Compared to placebo, clopidogrel significantly increased major bleeding (RR 1.38; 3.7% vs 2.7%; 95% CI 1.13-1.67). However, there was no significant excess of major bleeding in patients undergoing CABG surgery (RR 1.48; 1.3% vs 1.1%; 95% CI 0.93-1.71). The median time for clopidogrel discontinuation before CABG surgery was 5 days.Results from various subgroups are presented for the first primary composite endpoint and suggest the possibility of important treatment effect heterogeneity. Patients with a history of revascularization represented a minority of patients in the study (18%) and experienced higher rates of events but derived a significantly greater benefit from clopidogrel compared to those not previously revascularized (RR 0.58 vs 0.89).Patients >65 years of age made up about half of study participants, and experienced event rates >2x higher than those ≤65 years of age, but derived less benefit from clopidogrel (RR 0.87 vs 0.71). The same was true based on risk tertiles. Patients at low and intermediate risk of experiencing events based on risk scores, experienced similar risk reductions from clopidogrel of 76% and 69% respectively; however, those at the highest risk received less benefit (RR 91%). Finally, women appeared to benefit less than men (RR 89% vs 76%).Notably, there was no evidence of treatment effect heterogeneity based on whether patients underwent revascularization or not following randomization.During the trial, clopidogrel was discontinued temporarily (≥5 days) in 46% of patients mainly due to the need for a surgical procedure. A total of 21% of patients discontinued clopidogrel permanently compared to 18% in the placebo group.Conclusions In patients admitted to the hospital for unstable angina or NSTEMI, clopidogrel for 3-12 months plus aspirin, reduced the rate of a composite primary endpoint compared to aspirin alone and was associated with a number needed to treat of approximately 50 patients. This benefit was driven almost entirely by reducing nonfatal MI. Clopidogrel increased major bleeding with an NNH of approximately 100 patients.In our opinion, the benefit conferred by clopidogrel in this patient population is modest and the external validity is uncertain as no information is provided on patients enrolled compared to those who were eligible/screened. Patients with prior histories of revascularization derived the greatest benefit; however, several higher risk subgroups including older patients (>65 years of age) and the third of patients who were at the highest risk of experiencing events derived significantly less benefit. Women, also derived less benefit. In the groups less likely to benefit, we would expect them to experience higher rates of adverse events as well and thus, it is possible they derive no net benefit from clopidogrel or could even experience net harm.While thienopyridines have come to be considered a foundational treatment for ACS, evidence of their benefit from the CURE trial is modest at best; based mainly on reduction of a nonfatal endpoint.The CURE trial results should be translated cautiously, especially for patients who are older, frail and more susceptible to adverse events.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

JAMA 2001;285:1711-18.Background Statin therapy had been shown to improve blood cholesterol and improve long-term outcomes in patients with stable coronary artery disease with significant effects evident after 2 years of treatment. These early trials excluded patients with recent acute coronary syndromes and thus, the possibility of early benefit from statin therapy in this patient population was untested. But, patients with ACS are the most vulnerable to experiencing recurrent events in the early period following an initial event and certain physiologic effects of statins were theorized to be beneficial during this period. These effects included improvement in endothelial function, decreased platelet aggregation and thrombus deposition, and reduced vascular inflammation. The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study sought to test the hypothesis that early treatment with high dose atorvastatin in patients with unstable angina or non-Q-wave AMI would reduce early ischemic events and death.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 of experienced unstable angina or non-Q-wave AMI within the 24-hour period before hospitalization. The definition of unstable angina was strictly applied and in contemporary practice, all would meet criteria for NSTEMI. Patients were excluded for the following reasons: serum cholesterol >270 mg/dl but there was no lower limit; if coronary revascularization was planned or anticipated at the time of screening; evidence of Q-wave AMI within preceding 4 weeks; CABG surgery within the preceding 3 months; PCI within the preceding 6 months; left bundle branch block or paced rhythm; severe CHF; concurrent treatment with other lipid-lowering agents, vitamin E, drugs associated with rhabdomyolysis in combination with statins; severe anemia; renal failure requiring dialysis; hepatic dysfunction (ALT >2 ULN); insulin-dependent diabetes; pregnancy or lactation.Baseline characteristics The average age of patients was 65 years and two-thirds were men; 86% were white. Approximately one quarter of patients had a prior MI, 23% had non-insulin-dependent diabetes and 55% had hypertension. The average time to randomization from hospital admission was about 2.5 days. The inclusion event was unstable angina in 46% and non-Q-wave AMI in the remainder. Non-cholesterol lowering cardiac medicines were similar prior to, during and following the hospitalization index event.Procedures Between 24 and 96 hours after hospital admission, patients received either atorvastatin 80 mg per day or matching placebo for 16 weeks. Treating physicians were instructed not measure serum lipid levels in the local hospital laboratory during the study period. All patients received instruction and counseling on a low cholesterol diet. Patients were seen in follow-up 2, 6, and 16 weeks after initiation of therapy. Laboratory testing was performed centrally at baseline and at 6 and 16 weeks.Endpoints The primary endpoint was a composite of all-cause death, nonfatal MI, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence requiring emergency hospitalization. The recurrent ischemia endpoint required both exacerbation of the patient's usual symptoms and new objective evidence of ischemia with definite change from a comparison study performed after the index ischemic event. Secondary endpoints were occurrence of each component of the primary composite endpoint as well as nonfatal stroke; new or worsening heart failure requiring hospitalization, worsening angina requiring hospitalization but without objective evidence of ischemia, coronary revascularization, time to first occurrence of any primary or secondary endpoint, and percentage changes in blood lipid levels from baseline to 16 weeks.An initial sample size requirement of 2,100 was based on an assumption of a 20% primary composite event rate in the control group and 14% rate in the atorvastatin-treated group (17% overall rate), with an alpha of 0.05 and 95% power. The sample size was then increased to 3,000 upon the recommendation of the steering committee. This, after a blinded analysis of pooled data from the first 1,260 patients indicated the event rate was lower than anticipated (13% overall). A sample size of 3,000 would confer 95% power to detect a 30% relative treatment effect and 80% power to detect a 25% relative effect at an alpha of 0.05.Results 3,086 patients were included in the final analysis; 1,548 in the placebo group and 1,538 in the atorvastatin group. All patients were followed for 16 weeks. Compared to placebo, atorvastatin significantly reduced the risk of the primary composite endpoint (RR 0.84; 14.8% vs 17.4%%; 95% CI 0.70-1.00; p=0.048). For the individual components, there were no significant differences in death (4.2% vs 4.4%), nonfatal MI (6.6% vs 7.3%), or resuscitated cardiac arrest (0.5% vs 0.6%), but there was a statistically significant reduction in the endpoint of emergency rehospitalization for recurrent symptomatic ischemia (RR 0.74; 6.2% vs 8.4%; 95% CI 0.57-0.95).For the secondary endpoints, there were significant reductions in stroke in the atorvastatin group but this was based on a small number of events. Perhaps unexpectedly, there was a numerical increase in coronary revascularization procedures in the atorvastatin group despite there being a statistically significant reduction in emergency hospitalizations for recurrent ischemia as mentioned above.Data on subgroups was not presented.Compliance with prescribed study treatment was 86% in the atorvastatin group and 88% in the placebo group. Treatment was discontinued prematurely in 11.2% of the atorvastatin group compared to 10.3% in the placebo group. No serious adverse events occurred with a frequency of more than 1% in either group. An increase in LFTs (>3x ULN) occurred in 2.5% in the atorvastatin group and 0.6% of patients in the placebo group; 3 of these patients in the atorvastatin group were hospitalized with hepatitis and each case resolved following discontinuation of the drug. There were no documented cases of myositis.After 16 weeks, LDL cholesterol had increased by an adjusted mean of 12% to 135 mg/dl in the placebo group and decreased by an adjusted mean of 40% to 72 mg/dl in the atorvastatin group. Total cholesterol and triglycerides also decreased significantly in the atorvastatin group compared to placebo and there were no significant changes in HDL cholesterol.Conclusions In patients admitted to the hospital with non-Q-wave acute coronary syndromes, high dose atorvastatin significantly reduced a composite primary endpoint of cardiovascular events over the first 16 weeks of treatment with an NNT of 38; however, this was driven by a reduction in emergency hospitalizations for recurrent ischemia. There is no evidence from this trial that high dose statin therapy reduces the individual endpoints of death or nonfatal MI over this period; nor did it reduce coronary revascularization, which is counterintuitive given the significant increase in emergency hospitalizations for recurrent ischemia. Coronary revascularization events were twice as likely to occur as emergency hospitalizations.The external validity of the trial is limited by the restricted nature of the study population. Patients were excluded if revascularization was planned during initial admission, which in many places is the standard of care for ACS up to the present day. Furthermore, higher risk ACS subgroups were excluded, including patients with insulin-dependent diabetes, advanced heart failure and ESRD. The relatively unimpressive clinical benefit observed in MIRACL should not be assumed to extend to such patients. It would not be unreasonable to conclude that the results from MIRACL do not apply to the average patient with ACS in contemporary practice.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

Commentary by Dr. Valentin Fuster

Lancet 1996;347:561-68.Background In most of the prior AMI trials presented here, patients with non_ST-segment myocardial infarction (NSTEMI) and/or unstable angina were included with patients with ST-segment myocardial infarction (STEMI). Patients with NSTEMI usually represented about 1/3 of trial participants. It had become clear based on subgroup analyses from the previous trials that NSTEMI patients did not benefit from thrombolysis. So, while intravenous anticoagulation with heparin was not found to be beneficial in GISSI-2 or ISIS-3, where thrombolysis was also used, there remained the possibility that it may benefit patients with unstable coronary syndromes who were not candidates for thrombolytic therapy. This smaller trial represents a departure from the general eligibility criteria for the AMI trials that we have already reviewed. The Fragmin During Instability in Coronary Artery Disease (FRISC) study group sought to test the hypothesis that subcutaneous low-molecular-weight heparin, in combination with aspirin, reduces death and new cardiac events in patients with unstable CAD. For the purposes of this study, unstable CAD represents unstable angina and NSTEMI.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 had to be men older than 40 years and women at least 1 year after menopause admitted to the hospital for chest pain within the previous 72 hours. All patients had to have either newly developed or increased angina symptoms during the previous 2 months or persisting chest pain with suspicion for AMI and at least one of the following ECG criteria: transient or persistent ST depression of ≥ 0.1 mV or T-wave inversion of ≥ 0.1 mV in at least 2 adjacent leads without pathological Q waves in the ischemic leads. Essentially, the authors were selecting patients with unstable angina or NSTEMIs and not STEMIs or completed infarcts. There were many exclusion criteria for the trial including the presence of conditions with an increased risk of bleeding, known renal or liver insufficiency, indications for thrombolysis, suspected myocarditis and many others; however, it is worth noting there was no upper age limit.Baseline characteristics There were 5,137 patients who met eligibility criteria and 1,506 (29%) were randomized. The 3 most common reasons for exclusion were risk of bleeding (20%), compliance problems (15%), and Q waves or bundle branch block (14%). Patients with other severe disease accounted for 4% of exclusions and those with renal or liver insufficiency accounted for 2%.The median age of participants was 69 years and approximately 65% were men. 20% of participants were active smokers, 13% had diabetes and nearly 30% had a previous heart attack. Patients with NSTEMI accounted for close to 40% of participants and the remainder had unstable angina.Procedures Treatment was started as soon as possible after admission. During the first 6 days (acute phase), 120 IU per kg bodyweight (maximum dose of 10,000 IU) of dalteparin or placebo was injected every 12 hr. There was then a home treatment phase. For the next 35-45 days—at home— 7,500 IU of dalteparin or placebo was injected once daily. Patients stayed in the hospital during the acute phase for at least 5 days and on day 5-8 were discharged with the lower home dose. On day 40-50, the treatment was stopped and the final follow-up visit was scheduled 5-7 months after trial enrollment.Endpoints The primary endpoint was the rate of death and new myocardial infarction during the first 6 days. Secondary endpoints were the rates of death and new MI after 40 and 150 days, the frequency of revascularization procedures and need for heparin infusion, and a composite endpoint. Cause of death and myocardial infarction were verified by the independent endpoint committee who had to differentiate a new event from an inclusion event. Safety endpoints included major and minor bleeding. Major bleeding was defined by a drop of ≥2 g/dL in hemoglobin with associated signs or symptoms of bleeding, and minor bleeding was any other bleeding not meeting the former criteria. A sample size of 1,500 was based on a power of 0.80 to detect a reduction in the primary composite endpoint from 6% to 3% at a 2-sided alpha of 5%. Subgroup analyses were prespecified and a “high-risk group” was defined by the presence of at least 2 of the following variables: age >70, previous MI, medically treated heart failure, or diabetes.Results 1,506 patients were included in the final analysis; 757 in the placebo group and 741 in the dalteparin group. At 6 days, dalteparin significantly reduced the occurrence of the primary endpoint (RR 0.37; 1.8% vs 4.8%; 95% CI 0.20-0.68), which was driven by myocardial infarction (RR 0.33; 1.4% vs 4.4%; 95% CI 0.16-0.60). There was no difference in death between groups (RR 0.88; 0.9% vs 1.1%; 95% CI 0.32-2.48) and minor bleeding events were much more common in the dalteparin group (8.2% vs 0.3%).At 40 (8.0% vs 10.7%) and 150 (14.0% vs 15.5%) days, differences between groups were less pronounced for the primary endpoint and the results, in favor of dalteparin, were not statistically significant. Bleeding events, driven by minor bleeding, continued to be much higher for the dalteparin group.Subgroup analyses are presented at 6 and 40 days and are generally concordant across subgroups, meaning the treatment effect goes in the same direction, but these analyses should be viewed skeptically as they represent small sample sizes, particularly compared to subgroups in the earlier mega trials. Subgroup data suggests concordant results for patients less than or greater than 70 years of age and for patients meeting high risk criterion compared to those not meeting it.Conclusions In patients with unstable angina and NSTEMI, dalteparin reduced the primary endpoint of death or nonfatal MI compared to placebo at 6 days and was associated with a NNT of 33 patients. This was driven by a reduction in nonfatal MI. The results were no longer significant at 40 or 150 days. This trial is limited by small sample size and highly selected patient population.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

Lancet 1988;349-360Background The introduction to the ISIS-2 manuscript opens with a remarkable statement from the authors:Reductions in mortality that are realistically moderate (eg, “only” 20-25%) are important, especially if produced by widely practicable treatments for common causes of death.At the time of this posting, January 2024, it's amazing to think, how in 1988, a 20-25% reduction in mortality was considered moderate for a “widely practicable treatment for a common cause of death” and now the profession seems to grasp at almost anything, at nearly any cost, that reduces some composite of hard, soft and, in some cases, completely meaningless endpoints by the same amount. Regardless, ISIS-2 sought to test the hypothesis that streptokinase and aspirin, either alone or together, would reduce vascular mortality in patients with MI.Patients Patients with suspected myocardial infarction, who the responsible physician thought were within 24 hours of symptom onset and had no clear indication for, or contraindication to, streptokinase or aspirin. Absolute contraindications included: any history of stroke or of gastrointestinal ulcer. Possible contraindications included: recent arterial puncture, recent severe trauma, severe persistent hypertension, allergy to streptokinase or aspirin, low risk of cardiac death, or some other life-threatening disease. ECG changes at entry were not required.The design was meant to be pragmatic to facilitate patient enrollment; however, exclusion criteria was more extensive for ISIS-2 compared to ISIS-1, which reflects concern about hemorrhagic side effects associated with use of these agents. Like ISIS-1, there were no special procedures dictating patient follow-up after the hospitalization ended.Baseline characteristics Basic demographic information is not provided in the main manuscript but we can infer from the subgroup Forest plots that more than two thirds of patients were men, the overwhelming majority were less than 70 years of age, and nearly half were less than 60. Less than 20% had a previous MI and only around 7% had diabetes. Patients with inferior and anterior STEMI's composed more than half of the cohort. About 43% of patients presented within 4 hours of symptom onset, another 42% presented between 5 and 12 hours, and the remaining 15% presented between 13 and 24 hours.Procedures A 2x2 factorial study design was used. All patients were randomly assigned to receive either streptokinase or a matching placebo. All patients were also randomly assigned to receive either aspirin or a matching placebo. This led to 4 distinct treatment groups: 1) streptokinase + aspirin placebo, 2) aspirin + streptokinase placebo, 3) streptokinase + aspirin, or 4) placebo onlyPatients allocated to receive streptokinase were immediately given 1.5 MU of ‘Streptase' over 1 hour. Patients allocated to receive aspirin were immediately given 162.5 mg of an enteric coated tablet that was crushed, sucked, or chewed for a rapid anti-platelet effect. Thereafter, they took a 162.5 mg tablet daily for 1 month.Endpoints Vascular mortality over 5 weeks was the primary endpoint. Follow-up after discharge involved only mortality, through government records wherever possible.Results 17,187 participants were randomized from 417 hospitals in 16 countries. Compliance with the assigned treatments was estimated to be between 90-95%.The results of ISIS-2 are not reported in a standard results table, making vascular mortality as well as all-cause mortality impossible to infer over the duration of the trial. The number of non-vascular deaths are presented in a table but vascular deaths beyond 5 weeks are not formally provided in the original publication. The only evidence of vascular deaths beyond 5 weeks is presented in survival curves.Over 5 weeks, Streptokinase alone reduced vascular mortality compared to placebo by approximately 25% (9.2% vs 12.0%) and these results were highly significant. The difference remained highly significant over the course of the trial. Non-vascular deaths accounted for a tiny fraction of all deaths (3.5%) and were unchanged between groups. Subgroup analysis of streptokinase efficacy based on time from pain onset showed it was more effective if given within 4 hours (8.2% vs 12.3%) vs between 5-24 hours (10.0% vs 11.8%).Streptokinase use was associated with higher rates of hypotension and bradycardia (10% vs 2.0%), allergic reactions (4.4% vs 0.9%), minor bleeding (3.5% vs 1.0%) and major bleeding (0.5% vs 0.2%). The bleeding excess appeared similar whether streptokinase was used with aspirin or not. Streptokinase was also associated with a small but significant risk of cerebral hemorrhage (7 vs 0 events) all of which were followed by death or severe disability. However, overall, streptokinase was not associated with an increase in stroke (0.7% vs 0.8%) or in the risk of disabling/fatal stroke (0.5% vs 0.6%).Aspirin alone reduced vascular mortality compared to placebo by 23%, approximately the same amount as streptokinase alone over 5 weeks (9.4% vs 11.8%), and these results were highly significant and remained so over the course of the trial. There were fewer non-vascular deaths among aspirin allocated patients, so all-cause deaths were also significantly reduced but like with streptokinase, non-vascular death accounted for a tiny fraction of all deaths. Unlike Streptokinase alone, the treatment effect of aspirin was unchanged regardless of when it was started relative to the onset of pain.Aspirin significantly increased minor bleeds (2.5% vs 1.9%) but there were no major differences in any other side effects.Streptokinase and aspirin compared to double placebo reduced vascular mortality nearly twice as much as either agent alone (8.0% vs 13.2%) and these results were highly significant and remained so over the course of the trial. Non-vascular deaths were the same between groups and so all-cause mortality was also significantly reduced by streptokinase and aspirin. Subgroup analysis based on time from pain onset demonstrated greater efficacy for those receiving treatment in under 4 hours (6.4% vs 13.1%) compared to those receiving treatment between 5-24 hours (9.2% vs 13.3%).Streptokinase and aspirin together were associated with increases in major and minor bleeding as well as cerebral hemorrhage that were similar to streptokinase alone both in terms of their relative and absolute differences.Additional subgroup analyses suggest that patients presenting with anterior STEMI's derived the greatest benefit from streptokinase alone and in combination with aspirin. The risk of death was about twice as high for patients presenting with an anterior vs inferior STEMI (15% vs 8%). Patient's presenting with ST depression on their ECGs experienced a similar overall risk of death compared to patients with anterior STEMI's but did not appear to derive a significant benefit from any combination of treatment.Conclusions Streptokinase alone and aspirin alone reduced death over 5 weeks compared to placebo. 30 to 40 patients would need to be treated with either agent alone to prevent 1 person from dying, which was very similar to the effect noted in the GISSI trial that tested Streptokinase alone. In ISIS-2, the combination of the 2 agents (Streptokinase and Aspirin) reduced death even further (nearly twice the effect of either agent alone) compared to double placebo controls and this was associated with an NNT of 20 or less. Streptokinase, whether alone or in combination with aspirin, exerted the greatest effect when given to patients presenting within 4 hours from pain onset but was still effective when given outside this window (subgroup stratification was not the same as GISSI, which showed that the benefit waned and possibly reversed after 6-9 hours). In ISIS-2 there was no evidence to suggest that sicker patients or those with larger MI's did worse (i.e, lower SBP, higher HR, or anterior STEMI) but again, not all subgroups presented were the same as in the GISSI trial, which did show less benefit for some higher risk groups. Like GISSI, ISIS-2 provided evidence that patients presenting with NSTEMI's did not benefit from streptokinase.In summation, ISIS-2, like the GISSI trial that preceded it, demonstrated the significant impact of early revascularization via thrombolysis on mortality in patients presenting with STEMI. It also demonstrated the significant benefit of aspirin and the additive effect of both agents together. To this day, the pillars of STEMI management involve aspirin and prompt revascularization, whether done via thrombolysis or PCI.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

Take Home Points: All STEMIs should be loaded with dual antiplatelet therapy. Prasugrel (Effient) is avoided as there is an increase in bleeding complications if the patient requires a CABG. NSTEMI cases can be challenging to manage. Consult Cardiology early and use all available data. The appropriate medical treatment for ACS patients is as important ... Read more The post REBEL Core Cast 113.0 – ACS Therapies and Management appeared first on REBEL EM - Emergency Medicine Blog.

Two terms you've probably heard mentioned are STEMI and NSTEMI, and you may be wondering what the difference between these two cardiac events is. In this episode you'll learn:  The key differences between STEMI and NSTEMI How to recognize a STEMI on the ECG What “contiguous leads” actually means Signs and symptoms of myocardial infarction Tests utilize to diagnose and evaluate an MI How STEMI and NSTEMI are treated _________ Full Transcript - Read the article and view references FREE CLASS - If all you've heard are nursing school horror stories, then you need this class! Join me in this on-demand session where I dispel all those nursing school myths and show you that YES...you can thrive in nursing school without it taking over your life! Crucial Concepts Bootcamp - Start nursing school ahead of the game, or reset after a difficult first semester with my nursing school prep course, Crucial Concepts Bootcamp. Learn key foundation concepts, organization and time management, dosage calculations, and so much more.

What does it mean when they say you had a STEMI or NSTEMI? ST Elevation myocardial infarction versus non ST elevation myocardial infarction. https://dralo.net/links

This week, I talk with Andrew Foy, who is an academic cardiologist at Penn State University in Hershey, PA. Andrew is one of the smartest voices in medicine today. We start with the REMEDIAL trial, published recently in JAMA. Ablation vs Meds. Primary endpoint—depression and anxiety. One of the main issues was the control arm—namely that there was no sham control. We referenced this useful review paper on placebo and nocebo effects in cardiology, from Brian Olshansky. Our second topic was the FRAIL AF trial. This was frail, elderly patients who had AF and were stable on Vitamin K antagonists (similar to warfarin) were randomized to remain on the VKA or switch to a direct acting oral anticoagulant. Primary endpoint—major bleeding. FRAIL AF is in Andrew's wheelhouse as one of his primary academic areas of study is the role of multi-morbidity in translating medical evidence. He mentions a term called heterogenous treatment effects or HTE. I don't love the term because it's heavy into jargon. But HTE is super important for using evidence in the clinic. Andrew explains it well.Here is the editorial Andrew co-authored regarding another important trial in elderly patients who were having NSTEMI. I have written about FRAIL AF on Medscape and Sensible Medicine. We were going to talk about coronary artery calcium screening, but we had talked enough and will do a separate podcast on CAC. Sensible Medicine is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.As always, let us know what you think. We appreciate the support. Thank you. JMM This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

In this podcast, Dr. Steve Smith - an emergency medicine physician with Hennepin Healthcare and full faculty professor of Emergency Medicine at the University of Minnesota, discusses OMI (occlusion myocardial infarction) and NOMI (non-occlusion myocardial infarction) matrix, along with the importance of proper ECG interpretation and how this impacts the management of acute coronary syndrome. Dr. Smith also talks about STEMI and NSTEMI and the use (or the replacement) of these terms. Enjoy the podcast. Objectives:Upon completion of this podcast, participants should be able to: Express that acute coronary occlusion must be diagnosed and treated emergently. Recognize that ST elevation on the EKG is a very poor way of diagnosing occlusion myocardial infarction (OMI). Recognize that the entire QRST wave on the EKG is important for the diagnosis of occlusion mycardial infarction (OMI). Identify when other modalities (other than the EKG) may be needed to make a diagnosis of acute coroanary occlusion (OMI). Recognize that deep convolutional neural networks are the future of EKG diagnosis of acute coronary occlusion. This activity has been planned and implemented in accordance with the accreditation criteria, standards and policies of the Minnesota Medical Association (MMA). Ridgeview is accredited by the Minnesota Medical Association (MMA) to provide continuing medical education for physicians.  CME credit is only offered to Ridgeview Providers & Allied Health staff for this podcast activity. After listening to the podcast, complete and submit the online evaluation form. Upon successful completion of the evaluation, you will be e-mailed a certificate of completion within approximately 2 weeks. You may contact the accredited provider with questions regarding this program at Education@ridgeviewmedical.org. Click the link below, to complete the activity's evaluation. CME Evaluation (**If you are listening to the podcasts through iTunes on your laptop or desktop, it is not possible to link directly with the CME Evaluation for unclear reasons. We are trying to remedy this. You can, however, link to the survey through the Podcasts app on your Apple and other smart devices, as well as through Spotify, Stitcher and other podcast directory apps and on your computer browser at these websites. We apologize for the inconvenience.)  DISCLOSURE ANNOUNCEMENT  The information provided through this and all Ridgeview podcasts as well as any and all accompanying files, images, videos and documents is/are for CME/CE and other institutional learning and communication purposes only and is/are not meant to substitute for the independent medical judgment of a physician, healthcare provider or other healthcare personnel relative to diagnostic and treatment options of a specific patient's medical condition; and are property/rights of Ridgeview.  Any re-reproduction of any of the materials presented would be infringement of copyright laws.  It is Ridgeview's intent that any potential conflict should be identified openly so that the listeners may form their own judgments about the presentation with the full disclosure of the facts. It is not assumed any potential conflicts will have an adverse impact on these presentations. It remains for the audience to determine whether the speaker's outside interest may reflect a possible bias, either the exposition or the conclusions presented. Ridgeview's CME planning committee members and presenter(s) have disclosed they have no significant financial relationship with a pharmaceutical company and have disclosed that no conflict of interest exists with the presentation/educational event. Thank-you for listening to the podcast. SHOW NOTES:  *See the attachment for additional information.  Links:Steve Smith ECG Blog OMI Manifesto Please check out the additional show notes for more information/resources.

Master the prescription of antiplatelets and anticoagulation for coronary artery disease and afib (atrial fibrillation). We discuss why, when, and how long to prescribe aspirin, clopidogrel, ticagrelor, prasugrel, and/or anticoagulation for primary, secondary, and “primary and a half” prevention including the definition and discussion of mono, dual, and triple therapy for patients with coronary disease who need anticoagulation for atrial fibrillation. We're joined by preventive cardiologist, Dr. Donald Lloyd-Jones MD, ScM (@dmljmd from NMCardioVasc)! This episode was recorded in person at ACP's (@ACPIMPhysicians) Internal Medicine Meeting 2023 #im2023 in San Diego. Claim free CME for this episode at curbsiders.vcuhealth.org! Patreon | Episodes | Subscribe | Spotify | YouTube | Newsletter | Contact | Swag! | CME Show Segments Intro Getting to know our guest Definition mono, dual, triple therapy, DAPT Post-PCI for NSTEMI with existing afib Stable CAD with new Afib CABG with New Afib Prior stent with New Afib Antiplatelet therapy after Acute Coronary Syndrome Primary Prevention Primary “and a half” Prevention Life's Essential 8 Outro Credits Written and Produced by: Matthew Watto MD, FACP Show Notes: Matthew Watto MD, FACP Cover Art & Infographic: Matthew Watto MD, FACP Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP    Reviewer: Fatima Syed MD, MSc Showrunners: Matthew Watto MD, FACP; Paul Williams MD, FACP Technical Production: PodPaste Guest: Donal Lloyd-Jones MD, ScM

Its important as providers that we understand the heart and how it pumps our blood throughout the body. This episode talks about the mechanical function of the heart and school for thought on assessing these patients. With a growing population of cardiac patients, our goal is to figure out how we can provide the best care for these patients. The first step is always by learning. The more we know, the more we will be able to help our patients in a time of need. P.S. sorry for being sick. Informative Links:https://moosmosis.org/2020/07/09/circulatory-system-blood-flow-pathway-through-the-heart/https://pubmed.ncbi.nlm.nih.gov/11770070/https://www.mountsinai.org/health-library/diseases-conditions/hardening-of-the-arterieshttps://www.news-medical.net/health/Obesity-and-deep-vein-thrombosis-(DVT).aspx If you have any questions, comments, concerns, or a topic that you would like to be covered; feel free to reach out! Email: Emergencymedical101@gmail.comInstagram: https://instagram.com/healing_boost?igshid=YmMyMTA2M2Y=Support The Show!! ❤️https://www.buzzsprout.com/2090625/supporters/new

STEMI/NSTEMI and OMI/NOMI Paradigms Guest: Stephen W. Smith, M.D. Host: Anthony H. Kashou, M.D. Early detection of acute myocardial infarction (MI) can impact patients' immediate care and long-term outcomes. Most trained physicians can detect common ST-elevation MI (STEMI) patterns on ECG. However, a subset of patients does not present with common STEMI patterns. There are ECG patterns that can be identified to improve patient outcomes but are not yet widely known or accepted in current guidelines. Joining us today to discuss the STEMI versus non-STEMI (NSTEMI) and occlusion MI (OMI) versus nonocclusion MI (NOMI) paradigms is Stephen W. Smith, M.D., Emergency Medicine, Hennepin Healthcare, in Minneapolis. Specific topics discussed: The problem with the STEMI versus NSTEMI dichotomy Subgroup within the NSTEMI cohort that may benefit from emergent reperfusion therapy ECG findings to watch for — beyond, standard STEMI findings — that indicate an occluded artery Access to Dr. Smith's evaluation formula Patterns to watch for in diagnosis of OMI Benign mimickers Key takeaways for the novice interpreter Other clinical factors to watch for that may indicate OMI Recommendations for emergency medicine providers Connect with Mayo Clinic's Cardiovascular Continuing Medical Education online at https://cveducation.mayo.edu or on Twitter @MayoClinicCV. No CME available for this episode. Transcript found here. Original Release Date: 3/31/22

Myocardial infarctions can present in a variety of ways depending on vessel involvement, timing of pathology, and interpretation of diagnostics (e.g., 12-lead EKG). Unfortunately, not every patient with a myocardial infarction will fit STEMI criteria's paradigm, which has lead to the adoption of a new term: OMI (Occlusion Myocardial Infarction). In this podcast episode, we are joined by our very own Nick Zuber to discuss his recent OMI and why he's able to sit down and talk with us today. Get CE hours for our podcast episodes HERE! -------------------------------------------- Twitter @heavyhelmet Facebook @heavyliesthehelmet Instagram @heavyliesthehelmet Website heavyliesthehelmet.com Email contact@heavyliesthehelmet.com Disclaimer: The views, information, or opinions expressed on the Heavy Lies the Helmet podcast are solely those of the individuals involved and do not necessarily represent those of their employers and their employees. Heavy Lies the Helmet, LLC is not responsible for the accuracy of any information available for listening on this platform. The primary purpose of this series is to educate and inform, but it is not a substitute for your local laws, medical direction, or sound judgment. --------------------------------------------  Crystals VIP by From The Dust | https://soundcloud.com/ftdmusic Music promoted by https://www.free-stock-music.com Creative Commons Attribution 3.0 Unported License https://creativecommons.org/licenses/by/3.0/deed.en_US

Impact: Dyspnea vs. Chest Pain in the survival of NSTEMI patients

It's another session of CardioNerds Rounds! In these rounds, Dr. Priya Kothapalli (Interventional FIT at University of Texas at Auston, Dell Medical School) joins Dr. Deepak Bhatt (Dr. Valentin Fuster Professor of Medicine and Director of Mount Sinai Heart) to discuss the nuances of antithrombotic therapy. As one of the most prolific cardiovascular researchers, clinicians, and educators, CardioNerds is honored to have Dr. Bhatt on Rounds, especially given that Dr. Bhatt has led numerous breakthroughs in antithrombotic therapy. Come round with us today by listening to the episodes of #CardsRounds! Audio editing by CardioNerds Academy Intern, Dr. Christian Faaborg-Andersen. This episode is supported with unrestricted funding from Zoll LifeVest. A special thank you to Mitzy Applegate and Ivan Chevere for their production skills that help make CardioNerds Rounds such an amazing success. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds. Case details are altered to protect patient health information. CardioNerds Rounds is co-chaired by Dr. Karan Desai and Dr. Natalie Stokes.  Speaker disclosures: None Challenging Cases - Atrial Fibrillation with Dr. Hugh Calkins CardioNerds Rounds PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Show notes - Antithrombotic Management with Dr. Deepak Bhatt Case #1 Synopsis: A woman in her early 70s with a history of hypertension, hyperlipidemia, and paroxysmal atrial fibrillation presented with sudden-onset chest pressure and diaphoresis while at rest and was found to have an acute thrombotic 99% mid-LAD occlusion. The patient received OCT-guided PCI with a single drug-eluting stent. We discussed what the appropriate antithrombotic strategy would be for a patient with recent acute coronary syndrome and atrial fibrillation. Case #1Takeaways According to the recent 2021 revascularization guidelines, in patients with atrial fibrillation undergoing PCI and taking oral anticoagulant therapy, it is recommended to discontinue aspirin after 1 to 4 weeks while maintaining P2Y12 inhibitors in addition to a non-vitamin K oral anticoagulant or warfarin.There are two recent trials – AUGUSTUS and the ENTRUST-AF PCI trial – that evaluated regimens of apixaban and edoxaban, respectively, that support earlier findings reporting lower bleeding rates in patients maintained on oral anticoagulant plus a P2Y12 inhibitor compared to triple therapy.Of note, none of these trials were specifically powered for ischemic endpoints, but when pooling data from these trials, rates of death, MI and stent thrombosis with dual therapy were similar to those seen in patients on triple therapy.Additionally, all of these patients enrolled in these trials were briefly treated with triple therapy after PCI before the aspirin was discontinued. In the 2021 guidelines, it is noted that analyses of stent thrombosis suggest that 80% of events occur within 30 days of PCI. Thus, it is reasonable to consider extending triply therapy to 1 month after PCI in high risk patients to reduce risk of stent thromboses.In AUGUSTUS, 90% of patients received clopidogrel as their P2Y12 inhibitor Case #2 Synopsis: A man in his mid-50s with a history of peripheral vascular disease with prior SFA stent for chronic limb ischemia, hyperlipidemia, tobacco use, diabetes, and chronic kidney disease presented with a two day history of “reflux” that was worse with exertion and that improved with rest and associated with diaphoresis. He was diagnosed with an NSTEMI. His LHC revealed 99% mid-RCA thrombotic occlusion with moderate disease in the LAD. He underwent thrombectomy and PCI with a single drug-eluting stent to the RCA. We discussed his short-term and long-term antithrombotic therapy Case #2 Takeaways

Contributor: Travis Barlock, MD Educational Pearls: The presence of a STEMI has traditionally been used to determine if a patient with acute chest pain requires urgent cath lab management STEMI indicates an occluded coronary artery, and urgent intervention is needed to restore perfusion to ischemic tissue Patients with occluded coronary arteries can present with EKG findings other than STEMI 2022 ACC Expert Consensus Decision Pathway on the Evaluation and Disposition of Acute Chest Pain in the Emergency Department was recently published in the Journal of the American College of Cardiology Recognizes STEMI equivalents that necessitate cath lab management ST depression in precordial leads Indicates a posterior infarct/possible RCA occlusion LBBB c ST elevation meeting modified Sgarbossa criteria Hyperacute and/or De Winter T wave First indication of coronary artery occlusion Most beneficial time to initiate cath lab because more tissue is salvageable These recommendations will likely alter clinical practice for ED management of acute chest pain   References Kontos MC, de Lemos JA, Deitelzweig SB, et al. 2022 ACC Expert Consensus Decision Pathway on the Evaluation and Disposition of Acute Chest Pain in the Emergency Department: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. Oct 6 2022;doi:10.1016/j.jacc.2022.08.750 Meyers HP, Bracey A, Lee D, et al. Comparison of the ST-Elevation Myocardial Infarction (STEMI) vs. NSTEMI and Occlusion MI (OMI) vs. NOMI Paradigms of Acute MI. J Emerg Med. Mar 2021;60(3):273-284. doi:10.1016/j.jemermed.2020.10.026  Tziakas D, Chalikias G, Al-Lamee R, Kaski JC. Total coronary occlusion in non ST elevation myocardial infarction: Time to change our practice? Int J Cardiol. Apr 15 2021;329:1-8. doi:10.1016/j.ijcard.2020.12.082   Summarized by Mark O'Brien, MS4 | Edited by John Spartz, MD, & Erik Verzemnieks, MD In an effort to promote diversity, equity, and inclusion in Emergency Medicine, The Emergency Medical Minute is proud to present our 2nd annual Diversity and Inclusion Award. We support increasing the representation of underrepresented groups in medicine and extend this award to individuals applying to emergency medicine residencies during the 2022-2023 cycle. For information on award eligibility and the application process, visit https://emergencymedicalminute.com/edi-award/ Donate to EMM today!

Dr Edit Gara discusses Acute Coronary Syndrom, STEMI, NSTEMI and unstable angina.

Join Dr. Kolakalapudi and Dr. Buntaine as they review an interesting patient case and discuss the differential for NSTEMi with MRI findings. Links in the description are available for a more in depth review of clinical findings. https://www.ahajournals.org/doi/10.1161/JAHA.119.013757https://www.ncbi.nlm.nih.gov/books/NBK534808/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383353/https://www.ahajournals.org/doi/10.1161/CIR.0000000000000670

The Podcast crew is joined by MCHD In-Charge Paramedic Brady Walding to discuss a recent difficult STEMI case that intersected with Dr. Patrick in the ED. How do we best communicate with our consultants when we disagree? What happens when a paradigm shift is occurring without our consultants (STEMI vs. OMI/NOMI)? We are excited about our new Monday Morning Quarterback Series, where Dr. Patrick and Dickson review their cases with the MCHD medics involved. Hopefully, you will enjoy it as well!! REFERENCES 1. Meyers HP et al. Comparison of the ST-Elevation Myocardial Infarction (STEMI) vs. NSTEMI and Occlusion MI (OMI) vs. NOMI Paradigms of Acute MI. Journal of Emergency Medicine 2020. 2. https://www.nuemblog.com/blog/dont-forget-avl 3. https://www.youtube.com/watch?v=dWrG8d3YXq4

The following question refers to Section 4.9 of the 2021 ESC CV Prevention Guidelines. The question is asked by Dr. Christian Faaborg-Andersen, answered first by UCSD fellow Dr. Patrick Azcarate, and then by expert faculty Dr. Melissa Tracy.Dr. Tracy is a preventive cardiologist, former Director of the Echocardiography Lab, Director of Cardiac Rehabilitation, and solid organ transplant cardiologist at Rush University.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 #17 A 74-year-old man with a history of hypertension, chronic kidney disease, and gastroesophageal reflux presents with chest pain and is found to have an NSTEMI due to an obstructive lesion in the proximal LAD. One drug-eluting stent is placed, and he is started on dual antiplatelet therapy with aspirin and clopidogrel. He is concerned about the risk of bleeding from his gastrointestinal tract. What would you recommend to reduce his risk of bleeding? A. Lansoprazole, a proton pump inhibitorB. Famotidine, a histamine-2 blocker C. Calcium carbonate, an antacid D. None, proton pump inhibitors are contraindicated. Answer #17 The correct answer is A.The ESC recommends that patients at high risk for GI bleeding who are receiving antiplatelet therapy take proton pump inhibitors (Class I, LOE A). High risk for bleeding includes patients who are age ≥65, history of peptic ulcer disease, Helicobacter pylori infection, dyspepsia or GERD symptoms, chronic renal failure, diabetes mellitus, and concomitant use of other antiplatelet agents, anticoagulants, nonsteroidal anti-inflammatory drugs, or steroids.Coadministration of proton pump inhibitors that specifically inhibit CYP2C19 (omeprazole or esomeprazole) may reduce the pharmacodynamic response to clopidogrel. Although this interaction has not been shown to affect the risk of ischemic events, coadministration of omeprazole or esomeprazole with clopidogrel is not recommended.Main TakeawayIn patients with high gastrointestinal bleeding risk who are receiving antiplatelet therapy, proton pump inhibitors are recommended. Omeprazole and esomeprazole may reduce the efficacy of clopidogrel and should not be used concomitantly with clopidogrel.Guideline LocationSection 4.9.3, Page 3291Figure 13 page 3278; recommendation table page 3279. CardioNerds Decipher the Guidelines - 2021 ESC Prevention SeriesCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor RollCardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!

In this episode of EMplify: Conversation, Sam Ashoo, MD and TR Eckler, MD discuss high sensitivity troponin testing and clinical pathways.Topics discussed include: Which troponin assay are you currently using and what are its limits of detection? Do delta troponin results only count if they increase? If the test result is indeterminate, then what? repeat in 1 hr (European standard), repeat in 3 hours (depending on chest pain onset), or just admit if the HEAR(T) score is high? What does one negative troponin on presentation mean? No death in 30 days to 1 year but still missed MI?And more... ReferencesAnand A, et al; HiSTORIC Investigators†. High-Sensitivity Cardiac Troponin on Presentation to Rule Out Myocardial Infarction: A Stepped-Wedge Cluster Randomized Controlled Trial. Circulation. 2021 Jun 8;143(23):2214-2224. doi: 10.1161/CIRCULATIONAHA.120.052380. Epub 2021 Mar 23. PMID: 33752439; PMCID: PMC8177493.Chapman AR, et al. Association of High-Sensitivity Cardiac Troponin I Concentration With Cardiac Outcomes in Patients With Suspected Acute Coronary Syndrome. JAMA. 2017 Nov 21;318(19):1913-1924. doi: 10.1001/jama.2017.17488. Erratum in: JAMA. 2018 Mar 20;319(11):1168. Soerensen NA [corrected to Sorensen NA]. PMID: 29127948; PMCID: PMC5710293.Chenevier-Gobeaux C, et al. Multi-centre evaluation of recent troponin assays for the diagnosis of NSTEMI. Pract Lab Med. 2018 Feb 26;11:23-32. doi: 10.1016/j.plabm.2018.02.003. PMID: 30014015; PMCID: PMC6045566.Chiang CH, Chiang CH, Lee GH, Qian F, Chen SC, Lee CC. Time to Implement the European Society of Cardiology 0/1-Hour Algorithm. Ann Emerg Med. 2020 Nov;76(5):690-692. doi: 10.1016/j.annemergmed.2020.05.038. PMID: 33097132; PMCID: PMC7575504.McCarthy CP, Januzzi JL Jr. Increasingly Sensitive Troponin Assays: Is Perfect the Enemy of Good? J Am Heart Assoc. 2020 Dec;9(23):e019678. doi: 10.1161/JAHA.120.019678. Epub 2020 Nov 26. PMID: 33238785; PMCID: PMC7763764.Neumann JT, et al. Application of High-Sensitivity Troponin in Suspected Myocardial Infarction. N Engl J Med. 2019 Jun 27;380(26):2529-2540. doi: 10.1056/NEJMoa1803377. PMID: 31242362.Miller J, Cook B, Singh-Kucukarslan G, Tang A, Danagoulian S, Heath G, Khalifa Z, Levy P, Mahler SA, Mills N, McCord J. RACE-IT - Rapid Acute Coronary Syndrome Exclusion using the Beckman Coulter Access high-sensitivity cardiac troponin I: A stepped-wedge cluster randomized trial. Contemp Clin Trials Commun. 2021 Apr 23;22:100773. doi: 10.1016/j.conctc.2021.100773. PMID: 34013092; PMCID: PMC8114080.

Today we have Dr. Brian Locke back on to talk about asthma management and a new trial  of reliever-triggered inhaled glucocorticoids for Black and Latinx patients with asthma. Other questions we try to answer: Does methenamine prevent recurrent UTIs in women? Should CT coronary scan be done before invasive coronary angiography? Does melatonin prevent delirium in ICU patients? How good are patients at interpreting home COVID tests? What is the most common cause of type 2 NSTEMI? Give it a listen and find out! Reliever Triggered Inhaled Glucocorticoid Therapy in Black and Latinx Asthma PatientsMethenamine vs Antibiotics for Urinary Tract Infection Prophylaxis CT vs Invasive Coronary Angiography for Stable Chest Pain Melatonin for Delirium Prevention in ICU Patients Consumer Interpretation for At-Home COVID TestsBinax Rapid Test vs PCR for Sars-CoV-2 InfectionCharacteristics of Type 2 NSTEMIsMusic from Uppbeat (free for Creators!):https://uppbeat.io/t/soundroll/dopeLicense code: NP8HLP5WKGKXFW2R