Podcasts about evolocumab

Play Episode Listen Later Feb 3, 2025 62:46

Section 1: Introduction (0:00 - 5:30) Dr. Valentin Fuster introduces a special issue on Prevention, covering societal and individual prevention aspects and key cardiovascular risk factors. He highlights issues like medication adherence, obesity, and the need for better education and healthcare systems. Section 2: Prevention in Society (5:30 - 35:30) Adherence to Medications The PURE trial shows low medication adherence (31% at follow-up) across 17 countries, despite technological advancements in diagnostics. Barriers include low health literacy and inadequate healthcare systems. Social Determinants of Health Social deprivation leads to worse cardiovascular outcomes, especially among sexual minorities in the U.S. The editorial calls for more equitable healthcare access and anti-stigma efforts. Environmental Factors: Aircraft Noise Higher aircraft noise exposure is linked to worse heart health, urging noise reduction policies for vulnerable populations. Section 3: Prevention in Individuals (35:30 - 55:30) Sedentary Behavior Even with exercise, high sedentary time (over 10.6 hours a day) increases cardiovascular risk. Reducing sedentary time can significantly lower heart disease risk. Intensive Lifestyle Interventions for Diabetes Weight loss and lifestyle changes improve cardiac biomarkers and reduce cardiovascular risk in type 2 diabetes patients. Section 4: Risk Factor Impacts (55:30 - 1:10:00) Hyperlipidemia & Obesity Hyperlipidemia and obesity management, including medications like semaglutide, play key roles in preventing cardiovascular disease. The 2024 ESC hypertension guidelines are also crucial in risk reduction.

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JACC: Heart Failure - Randomized Trial of Cholesterol Lowering With Evolocumab for Cardiac Allograft Vasculopathy in Heart Transplant Recipients

JACC Speciality Journals

Play Episode Listen Later Nov 18, 2024 2:55

JACC Heart Failure Associate Editor Sean Pinney, MD, discusses a recently published original research paper that explores the results of a randomized controlled trial to test whether evolocumab reduces the burden of cardiac allograft vasculopathy.

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Long-Term Efficacy of Evolocumab In Patients With Or Without Multivessel Coronary Disease

Play Episode Listen Later Feb 5, 2024 8:19

Commentary by Dr. Valentin Fuster

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Episode 135: osteoporosis treatment, evolocumab, mifepristone for adenomyosis, and ambulatory BP

Primary Care Update

Play Episode Listen Later Aug 16, 2023 32:33

This week, Kate, Gary, Mark and Henry discuss treatments for osteoporosis in post-menopausal women, the effect of adding evolocumab to a statin - a reanalysis of the FOURIER trial, using mifepristone for painful adenomyosis, and real world data comparing 24-hour ambulatory BP with clinic readings.

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Jan 6 2023 This Week in Cardiology

This Week in Cardiology

Play Episode Listen Later Jan 6, 2023 23:59

Damar Hamlin, obesity and semaglutide, Open Data and PCSK9 inhibitors, and TAVI vs SAVR trials are the topics John Mandrola, MD, discusses in this week's podcast. This podcast is intended for healthcare professionals only. To read a partial transcript or to comment, visit: https://www.medscape.com/twic I. Damar Hamlin Five Thoughts on the Damar Hamlin Collapse https://www.medscape.com/viewarticle/986550 II. Semaglutide and Obesity in Adolescents FDA Approves Wegovy (Semaglutide) for Obesity in Teens 12 and Up https://www.medscape.com/viewarticle/986403 • Once-Weekly Semaglutide in Adolescents with Obesity https://www.nejm.org/doi/full/10.1056/NEJMoa2208601 III. Open Data and PCSK9 inhibitors Evolocumab Added to Statins Cuts CV Events in FOURIER Trial https://www.medscape.com/viewarticle/877348 • Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: a reanalysis based on regulatory data https://bmjopen.bmj.com/content/12/12/e060172 • Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease https://www.nejm.org/doi/full/10.1056/nejmoa1615664 • PCSK9 deficiency rewires heart metabolism and drives heart failure with preserved ejection fraction https://pubmed.ncbi.nlm.nih.gov/34252181/ • Bendary Tweet https://twitter.com/DrBendary/status/1609849852979986432?s=20&t=FDDhGIofS_HQ4jxf8aHwBA IV. Open Data and TAVI vs SAVR Trials Risk of Bias in Randomized Clinical Trials Comparing Transcatheter and Surgical Aortic Valve Replacement https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2799937 You may also like: Medscape editor-in-chief Eric Topol, MD, and master storyteller and clinician Abraham Verghese, MD, on Medicine and the Machine https://www.medscape.com/features/public/machine The Bob Harrington Show with Stanford University Chair of Medicine, Robert A. Harrington, MD. https://www.medscape.com/author/bob-harrington Questions or feedback, please contact news@medscape.net

Pragmatic Clinical Trials and EVOLVE-MI with Dr Christopher Cannon

Future Pulse Cardiology

Play Episode Listen Later Dec 12, 2022 21:01 Transcription Available

Dr Christopher Cannon discusses the potential of Pragmatic Clinical Trials in our research armamentarium with Dr. Thomas Nero. They review the EVOLVE-MI trial for Early use of Evolocumab after Myocardial Infarction in detail and highlight the potential for future research.

evolve clinical trials pragmatic myocardial infarction evolocumab

Circulation October 11, 2022 Issue

Play Episode Listen Later Oct 10, 2022 19:36

This week, please join author Michelle O'Donoghue and Associate Editor Parag Joshi as they discuss the article "Long-Term Evolocumab in Patients With Established Atherosclerotic Cardiovascular Disease." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts, Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, Associate Editor and Director of the Poly Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, very interesting feature this week. Evolocumab, another application for that in patients with established atherosclerotic cardiovascular disease. But before we get to that feature discussion, how about we grab a cup of coffee and discuss some of the other very interesting articles in this issue? Dr. Carolyn Lam: Oh, I'd love that. And I'd like to go first, because Craig, have you heard of hybrid debranching repair? I know, I know. I had that same look, and can I tell you about it? Because I found it so interesting. Dr. Greg Hundley: Absolutely. Dr. Carolyn Lam: Now, the management of complex aortic aneurysmal disease involving the visceral vessels is challenging due to its very high morbidity and mortality. After four decades of experience in open repair, only a few centers worldwide report laudable results. And numerous factors limit total endovascular repair, including the access to devices, experience in deploying them, and several anatomical restrictions. So, hybrid debranching procedures were introduced for those patients who are unfit for the open or endovascular excluded patients. And while these have been developed, small series have only been done and revealed a wide range of short term results. So, today's paper is very important, and it's from Dr. Oderich from UT Memorial Herman Texas Medical Center and colleagues. It's a large multi-institutional study, which contains the five year outcomes in 200 patients offering greater clarity in the usefulness and limitations of these hybrid debranching repair procedures. What they found was that hybrid aortic debranching had a low early mortality when done in lower risk patients, but mortality remained very elevated in high risk patients. And so, this suggests that deep branching could be a good alternative in patients adequate for traditional open repair, although pulmonary complications are quite common. The bypass grafts to the visceral vessels had very good patency with a five year primary patency of 90%. Permanent spinal cord injury occurred in 6%, suggesting that deep branching in experienced centers may offer outcomes comparable to centers of excellence for open thoracoabdominal aortic aneurysm repair. Dr. Greg Hundley: Wow, Carolyn, very nice and so beautifully explained. Dr. Carolyn Lam: You know what, Greg? I'm on a roll and I'd like to tell you about one more, this time a preclinical study. First, a little bit about the background. You see, transplantation with pleuripotent stem cell derived cardiomyocytes, as we know, represents a very promising therapeutic strategy for cardiac regeneration. We even have first clinical studies in humans, but yet little is known about the mechanism of action underlying graft induced benefits. So in this paper from Dr. Weinberger from University Medical Center Hamburg in Germany and colleagues, they explored whether transplanted cardiomyocytes actually actively contribute to heart function by injecting these cardiomyocytes with an optogenetic off on switch in a Guinea pig cardiac injury model. Dr. Greg Hundley: Wow, Carolyn, this is so interesting. So what did they find? Dr. Carolyn Lam: So, light induced inhibition of endo-grafted cardiomyocyte contractility resulted in a rapid decrease in left ventricular function in about 50% of the animals that was fully reversible with the offset of photo stimulation. So in conclusion, this optogenetic approach demonstrated that transplanted cardiomyocytes can actively participate in heart function, supporting the hypothesis that the delivery of new force generating myocardium can serve as a regenerative therapeutic strategy. Dr. Greg Hundley: Oh wow, Carolyn. That was just fascinating. Such incredible preclinical science in our journal. Well, Carolyn, this next paper comes to us from the world of myocarditis. And Carolyn, it involves a population based cohort of 336 consecutively recruited patients with acute myocarditis enrolled in both London and Maastricht. And the authors, led by Dr. Sanjay Prasad from Royal Brompton Hospital, investigated the frequency and clinical consequences of dilated cardiomyopathy and arrhythmogenic cardiomyopathy genetic variants in this population based cohorts of patients with acute myocarditis. Now, Carolyn, all participants underwent targeted DNA sequencing for well characterized cardiomyopathy associated genes and their comparison to healthy controls, of which they had 1,053 that were sequenced on the same platform. Case ascertainment of their outcomes in England was assessed against their national hospital admission data, and the primary outcome was all cause mortality. Dr. Carolyn Lam: So what did they find, Greg? Dr. Greg Hundley: Right, Carolyn. So these authors identified for dilated cardiomyopathy or arrhythmogenic cardiomyopathy associated genetic variants in 8% of patients with acute myocarditis. This was dominated by the identification of desmoplakin truncating variants in those with normal LVF, and then titin truncating variants in those with a reduced LVF. So Carolyn, importantly, these variants have clinical implications for treatment, risk stratification, and family screening. Genetic counseling and testing would be considered in patients with acute myocarditis to help reassure the majority of individuals that don't have one of these genes, while improving the management of those that do have one of the underlying genetic variants. Very interesting findings from the world of myocarditis. Dr. Carolyn Lam: Great. And a great clinical take home message. Thank you, Greg. Well, this next paper sought to investigate the influence of age on the diagnostic performance of cardiac troponins in patients presenting with suspected myocardial infarction. Dr. Atul Anand from the BHF Center for Cardiovascular Science and University of Edinburgh and colleagues did this by performing a secondary analysis of the high stakes stepped wedge cluster randomized control trial that evaluated the implementation of a high sensitivity cardiac troponin ISA in consecutive patients presenting with suspected acute coronary syndrome. Dr. Greg Hundley: Oh wow. Carolyn. Super interesting, and very applicable clinically. So what did they find here? Dr. Carolyn Lam: In older patients presenting with suspected MI, the majority of cardiac troponin elevations are explained by acute or chronic myocardial injury or type two MI. The specificity and positive predictive value of high sensitivity cardiac troponin to identify myocardial infarction decreases with age and is observed, whether applying sex specific or age adjusted 99th percentile diagnostic thresholds or a rolling threshold for the triage of patients at high probability of myocardial infarction. Serial troponin testing incorporating an absolute change in troponin concentration increased the discrimination for myocardial infarction in older adults. Dr. Greg Hundley: Oh wow, Carolyn. Such clinically applicable findings in this particular study, particularly when managing our aging population. Well, Carolyn, how about we discuss some of the other articles in this issue. And there's a very nice In-depth piece by our own Sami Viskin entitled “Arrhythmogenic Effects of Cardiac Memory.” And then, there's an exchange of letters by Drs. Giannitsis and Mueller regarding the article, “Unexpected Sensitivity Issue of Three High Sensitivity Cardiac Troponin I-Assays in Patients with Severe Cardiac Disease and Chronic Skeletal Muscle Diseases.” Dr. Carolyn Lam: Nice. There's also a Research Letter by Dr. Szendroedi on “Impaired Mitochondrial Respiration in Humans with Prediabetes: A Footprint of Prediabetic Cardiomyopathy.” And there's a CV case series by Dr. Kalra on very high cholesterol mimicking homozygous familial hypercholesterolemia. Interesting case. Well, I suppose that wraps it up. Let's go on to the feature discussion, shall we, Greg? Dr. Greg Hundley: You bet. Evolocumab. Welcome listers to this feature discussion on October 11th, and we're very fortunate today. We have with us Dr. Michelle O'Donoghue from Brigham Women's Hospital and Dr. Parag Joshi from UT Southwestern, the Associate Editor for this paper. Well, Michelle, can you describe for us some of the background information that went into the preparation of your study, and then what was the hypothesis that you wanted to address? Dr. Michelle O'Donoghue: Sure. Happy to do so, and thank you for having me. So by way of background, the Fourier study, which was previously published in the New England Journal, compared Evolocumab to placebo in 27,000 plus patients with established atherosclerotic cardiovascular disease, and Evolocumab significantly reduced the risk of major adverse cardiovascular events. But, the follow up duration was relatively short. Median follow up was 2.2 years. So this was now an open label extension study to Fourier known as the Fourier OLE study that allowed an additional median follow up time of five years, during which time all patients were now treated with open label Evolocumab. T. He primary hypothesis that we were testing in this extension study was primarily to look at long term safety. We had limited data to really assure us of the safety of PCSK9 inhibitors over the course of several years. And so, safety was the primary hypothesis that we were testing, but also of course of key interest, during the parent Fourier study, we know that the benefit for cardiovascular risk reduction appeared to grow over time. So this was also an opportunity to see that pattern and to see whether or not there was in fact legacy effect for patients who were treated earlier with Evolocumab versus placebo. Dr. Greg Hundley: Very nice, Michelle. And so, sounds like we have a substudy of the Fourier trial. Can you describe for us a little bit more, for this substudy, your study population and your study design? Dr. Michelle O'Donoghue: Sure. So the patients enrolled in the open label extension were a subset of those who participated in the parent study. So as I previously mentioned, more than 27,000 participated in Fourier. It was a global study. For the open label extension, it was more than 6,500 patients who participated, and those were patients who were at sites in Europe and United States. And so, those patients were then followed on average for a meeting of five years. So that means that all together, patients who had been randomized to Evolocumab in the parent study had potentially more than eight years of drug exposure for us to examine safety. Dr. Greg Hundley: Very nice. And so, what did you find? Dr. Michelle O'Donoghue: Well, first, looking at the first hypothesis of safety, we saw no evidence that there was any increased risk of any adverse events of interest when it comes to PCSK9 inhibitors as a drug class, or achieving very low levels of LDL cholesterol. So there was no uptick in terms of neurocognitive events, the risk of diabetes. We do know that there was an increased risk of injection site reactions with the PCSK9 inhibitors, but not one that appeared to persist over time. So first was the safety, but importantly, I think that the more interesting results perhaps were those for MACE, for cardiovascular risk reduction. So we saw, even though all patients were being treated with open label Evolocumab during the extension phase, the benefit that was seen during the parent study persisted. So there was a 15% reduction in the primary outcome, a broad composite of cardiovascular events. There was also a 20% reduction in the triple composite of cardiovascular death, MI, or stroke. And then perhaps of the most interest to your listeners is that there was a 23% reduction in cardiovascular mortality, and that was not something that was seen in the parent study. It really took time for that mortality benefit to emerge. Dr. Greg Hundley: Very nice. Michelle. Just a couple quick clarification points. Did you see these effects in both men and women? And then was there any impact of age on those results? Dr. Michelle O'Donoghue: Great questions. Some of those subgroup analyses are still ongoing, but no, we did not see any evidence of effect modification at first pass. But again, we'll be continuing to dig into all potential subgroups. Dr. Greg Hundley: Very nice. Parag, I know you have many papers come across your desk. What attracted you to this particular manuscript? Dr. Parag Joshi: Yeah, thanks. And congratulations again, Michelle. It's a really phenomenal study, and the findings, as you highlighted, are just really impactful for the field. I think for our journal at circulation, this is a really high impact finding in terms of extending out, giving us a rigorous way to look at long term follow up for people on PCSK9 inhibitors and really reassure that there is safety there. And as you highlighted, a sustained reduction in LDL cholesterol, other compounds in the space, Bococizumab in particular, that there were induced antibodies against the monoclonal antibody, and that sustained response was not there. So I thought that was also really reassuring, that over the course of eight years, we see sustained LDL reduction. And with that, really reaffirming the idea that the longer you can reduce LDL, there's an associated reduction in events. And as you highlighted, the initial Fourier, there was some question about why there wasn't a CV death mortality signal while there was in the Odyssey outcome study and slightly different patient populations of course, but just really needed more time to start to tease that out. So all of this, I think this is the first that we're seeing this kind of long-term data on this impactful class of medications that really made this a fantastic manuscript for us at Circulation. Dr. Greg Hundley: Wow. Boy, Parag, I don't know that you could have stated that any better. So Michelle, looking forward, what is your group thinking? And then maybe just as your comment on the field in general, what do you think is the next study or series of studies that needs to be performed in this sphere of research? Dr. Michelle O'Donoghue: Well, I think he started to touch upon the areas of interest to us, is that I think that there are still many opportunities to answer more questions even within this existing data set. In particular, there was a dedicated neurocognitive substudy that was built into the parent study. And we also have that now through the extension period. So, that was a sort of more rigorous assessment of neurocognitive outcomes. And so, that's another analysis that we're going to be pursuing in the near future and I think is of potential key interest. And then beyond that, I think that the PCSK9 inhibitor class in general is just so interesting. There are additional compounds that are under study, such as small interfering RNA, so different mechanisms of getting to the PCSK9 protein. And I think it'll be reassuring to see whether or not they are consistent results, regardless of how you lower PCSK9, whether it translates into similar types of clinical benefit. So I think it's an exciting field. And then stay tuned. I think there'll be more to come. Dr. Greg Hundley: Parag, do you have anything to add? What do you see really as the next series of studies that might be performed here in this area of research? Dr. Parag Joshi: Yeah, I think Michelle hit the nail on the head that seeing confirmatory evidence here would be great. And then really, what's so exciting about this space is there's so much interest in ways to address this protein, including gene editing, vaccination against it. And now you're getting the necessary evidence that, hey, you can really suppress these levels in patients for years without concerning safety signals, at least from what we've seen so far. So that's more excitement as to long term ways to address cardiovascular risk. Dr. Greg Hundley: Wow. Well, listeners, we've been very fortunate today to have with us Dr. Michelle O'Donaghue from Brigham and Women's Hospital, and Dr. Parag Joshi from UT Southwestern as the Associate Editor of Circulation to really bring us these exciting results, highlighting that long term LDL-C lowering with Evolocumab was associated with persistently low rates of adverse events over eight years that did not exceed those observed in the original placebo arm during the parent Fourier study, and led to further reductions in cardiovascular events compared with delayed treatment initiation. Well, on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week on the run. Dr. Greg Hundley: This program is copyright of the American Heart Association 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

Sept 16, 2022 This Week in Cardiology Podcast

This Week in Cardiology

Play Episode Listen Later Sep 16, 2022 23:37

The safety of very low LDL-C, the win-ratio analytic method, sacubitril/valsartan, SGLT2 inhibitors, and percutaneous left atrial appendage closure are discussed in this week's podcast. This podcast is intended for healthcare professionals only. To read a partial transcript or to comment, visit: https://www.medscape.com/twic I PCSK9I Evolocumab Benefits Accrue With Longer Follow-up: FOURIER OLE https://www.medscape.com/viewarticle/979950 - Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease https://www.nejm.org/doi/full/10.1056/nejmoa1615664 - Long-Term Evolocumab in Patients with Established Atherosclerotic Cardiovascular Disease https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.061620 II Analytic Methods and Re-Analysis of Old Trials - PARADISE-MI Results Obscured As Post Hoc Analysis Finds Flaws https://www.medscape.com/viewarticle/980776 - Angiotensin Receptor–Neprilysin Inhibition in Acute Myocardial Infarction https://www.nejm.org/doi/10.1056/NEJMoa2104508 - Impact of Sacubitril/Valsartan Versus Ramipril on Total Heart Failure Events in the PARADISE-MI Trial https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.057429 - The Year's Most Important Study Adds to Uncertainty in Science https://www.medscape.com/viewarticle/904286 III SGLT2i Post MI - Early Signal of Benefit for Empagliflozin in Acute MI: EMMY https://www.medscape.com/viewarticle/980180 - Empagliflozin in acute myocardial infarction: the EMMY trial https://doi.org/10.1093/eurheartj/ehac494 IV Percutaneous Left Atrial Appendage Closure - Incidence and Predictors of Early Death in Patients Undergoing Percutaneous Left Atrial Appendage Closure https://www.jacc.org/doi/10.1016/j.jacep.2022.06.012 - Cost‐Effectiveness of Left Atrial Appendage Closure for Stroke Reduction in Atrial Fibrillation: Analysis of Pooled, 5‐Year, Long‐Term Data https://www.ahajournals.org/doi/10.1161/JAHA.118.011577 - Baseline Comorbidities And Bleeding Events Of Patients Undergoing Percutaneous Left Atrial Appendage Occlusion Among Medicare Beneficiaries https://www.jacc.org/doi/10.1016/S0735-1097%2822%2901158-5 You may also like: Medscape editor-in-chief Eric Topol, MD, and master storyteller and clinician Abraham Verghese, MD, on Medicine and the Machine https://www.medscape.com/features/public/machine The Bob Harrington Show with Stanford University Chair of Medicine, Robert A. Harrington, MD. https://www.medscape.com/author/bob-harrington Questions or feedback, please contact news@medscape.net

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Circulation August 30, 2022 Issue

Medscape InDiscussion: Dyslipidemia

Play Episode Listen Later Aug 29, 2022 19:03

This week, please join author Rod Stables and Associate Editor Nick Mills as they discuss the article "Routine Pressure Wire Assessment Versus Conventional Angiography in the Management of Patients With Coronary Artery Disease: The RIPCORD 2 Trial." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast, summary and backstage pass through the journal and its editors. We're your co-hosts! I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, Associate Editor, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, this week's feature... Very interesting. There is a lot of information about using fractional flow reserve during contrast coronary angiography. But how does that compare to just reviewing the angiograms when managing patients with coronary artery disease? Well, we are going to hear some results from the RIPCORD 2 trial, and they may surprise you a little bit. But, before we get to that interesting feature discussion with authors and editors, how about we grab a cup of coffee and dive into some of the other articles in the issue? Dr. Carolyn Lam: Yeah, let's do that, Greg. Do you have a paper to share first? Dr. Greg Hundley: Oh, thanks Carolyn. Sure. So Carolyn, as we know, Apolipoprotein B or apoB, provides an integrated measure of atherogenic risk. But whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndromes, beyond that provided by low density, lipoprotein cholesterol, or LDLC, that's uncertain. So Carolyn this study emanates from the Odyssey Outcomes trial, which compared the Proprotein Convertase Subtilisin/Kexin Type 9 inhibitor, Evolocumab with placebo in 18,924 patients with recent ACS and elevated atherogenic lipoproteins despite optimized statin therapy. Now the primary outcome was major adverse cardiovascular events. So MACE was coronary heart disease, death, nonfatal myocardial infarction, fatal non-fatal ischemic stroke, and hospitalization for unstable angina. And associations between baseline ApoB or ApoB at four months and MACE were assessed in adjusted Cox proportional hazards and propensity score matched models over median of 2.8 years. Dr. Carolyn Lam: Oh, right. So what were the results, Greg? Dr. Greg Hundley: Right, Carolyn so impatience with recent ACS and elevated atherogenic lipoproteins, MACE increased across baseline ApoB strata, and now evolocumab reduced MACE across all strata of baseline ApoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved ApoB was associated with lower risk of MACE, even after accounting for achieved LDLC or Non-HDLC indicating that ApoB provides incremental information. And therefore, Carolyn, if it is modified achievement of an ApoB level less than or equal to 35 milligrams per deciliter may reduce lipoprotein attributable residual risk after ACS. Isn't that interesting? Dr. Carolyn Lam: Yes. Very nice, Greg. Thank you. This next paper is a pre-specified analysis of the EMPEROR-Preserved trial, looking at patients with and without diabetes. Dr. Greg Hundley: So remind us, Carolyn, what was the EMPEROR-Preserved trial and what did it show? Dr. Carolyn Lam: Well, in EMPEROR-Preserved Empagliflozin, the SGLT2 inhibitor reduced risk of the composite of cardiovascular death or heart failure hospitalization, as well as first and recurrent heart failure hospitalizations and slowed renal function decline in patients with heart failure and an ejection fraction greater than 40%. So the current paper sought to determine if effects were consistent in patients with, and without diabetes, of the almost 6,000 patients enrolled, 49% had diabetes. The risk of adverse outcomes, first of all, was higher in patients with diabetes. Now the treatment effect of Empagliflozin was however, similar in that Empagliflozin reduced the rate of the primary outcome and total heart failure hospitalization, irrespective of diabetes status. The effect of Empagliflozen falls into attenuate GFR decline, however, was also present in patients with, and without diabetes, although more pronounced in patients with diabetes. Now across all these three endpoints, the effect of Empagliflozen did not differ in patients with prediabetes or normal glycemia. And importantly, there was no increased risk of hypoglycemic events in either subgroup compared with placebo. So a very nice paper there. And that was from Dr. Gerasimos Filippatos from Athens University Hospital Attikon and colleagues. Dr. Greg Hundley: Wow, Carolyn, just really interesting information coming out of the world of SGLT2 innovation. Well, Carolyn, my next paper comes to us from the world of preclinical science and it's from Dr. Kunhua Song from the University of Colorado Anschutz Medical campus. So Carolyn, abnormalities of calcium homeostasis are closely associated with cardiac arrhythmias and heart failure and conditions that cause death of millions of people every year. Now, Carolyn Triadin physically interacts with the Ryanodine receptor 2 and plays an important role in releasing calcium from the sarcoplasmic reticulum to increase the free intracellular calcium concentration in cardiomyocytes. Now alternative splicing of a single Triadin gene produces multiple Triadin isoforms, the predominant cardiac Triadin isoform mouse Mt1 or human Trisk 32 is encoded by Triadin exons from one to eight. In humans, mutations in the Triadin gene that lead to a reduction in Trisk 32 levels in the heart cause cardiac dysfunction, cardiac arrhythmias and sudden death. Decreased levels of Trisk 32, in the heart, are also common in patients with heart failure. However, mechanisms that regulate alternative splicing of the Triadin gene to maintain levels of cardiac Triadin protein in the heart, remains somewhat elusive. Dr. Carolyn Lam: Wow. I am always learning from these cool papers. Thanks Greg. So what were the results? Dr. Greg Hundley: So Carolyn, the investigators found several things. First, the cardio MyoSite specific long non-encoding RNA or link RNA Triadin AS is essential for maintenance of cardiac function, exercise capacity and normal lifespan and Triadin AS knockout mice were found predisposed to cardiac arrhythmias in response to catecholamine challenge. And finally Carolyn, Triadin AS controls, levels, of cardiac Triadin isoforms, by regulating the splicing of the Triadin gene. Dr. Carolyn Lam: Oh, wow. All right. So could you bring it home for us, Greg? What are the clinical take home messages? Dr. Greg Hundley: Right, Carolyn. So cardiac explants from human heart failure patients as well as patients with cardiac arrhythmias, demonstrate reduced expression of Triadin AS and Triadin. And then next the mechanism of the Triadin AS and Triandin AS mediated alternative splicing of the Triadin gene to specifically control levels of cardiac isoforms of Triadin in the heart, provides a potential strategy for the treatment of cardiac arrhythmias and heart failure. Dr. Carolyn Lam: Wow. Thank you, Greg. Well, let's talk about what else is in today's issue. There's a Research Letter by Dr. Agarwal on Chlorthalidone for resistant hypertension and advanced chronic kidney disease. Dr. Greg Hundley: And Carolyn, I've got a perspective piece by Professor Cowie pertaining to atrial fibrillation entitled, “I'm Sorry, Mrs. Jones, but We Cannot Make You Feel Better Today.” Well, Carolyn, how about we get onto that feature discussion and review the utility of fractional flow reserve measurements, in patients undergoing contrast coronary angiography. Dr. Carolyn Lam: Great, let's go. Dr. Greg Hundley: Welcome listeners to this August 30th feature discussion. And we have with us this afternoon, Dr. Rod Staples from Liverpool and our own associate editor, Dr. Nick Mills from Edinburgh, Scotland. And gentlemen, welcome, Rod we'll start with you. Can you describe for us the background information that went into the preparation of your study and what was the hypothesis that you wanted to address? Dr. Rod Staples: Okay, well thanks very much for hosting today. I'm very grateful to be working circulation on this. I'm working with my co-lead investigator Professor Nick Harrison from Southampton, who's been doing an enormous amount of work on coronary physiology. He actually did the original RIPCORD study, what I suppose we'd now call RIPCORD 1, but it was called RIPCORD in the early days, an observational study that showed that systematic use of fractional flow reserve at the time of diagnostic angiography. Assessing the functional significance measured in each of the major coronary vessels, appeared in an observational study to have a dramatic effect on the subsequent management plans allocated to patients. And we decided to test this in a prospective randomized trial. Dr. Greg Hundley: Very nice. And so the exact hypothesis that you were going to test was what? Dr. Rod Staples: At the time of coronary angiography, a strategy of systematic measurement of fractional flow reserve in each and every coronary vessel, large enough to be considered for revascularization, would improve outcomes compared to a strategy based on angiographic assessments alone. Dr. Greg Hundley: Very nice. And so you mentioned a randomized trial. Can you describe further your study design and then which study population did you include? Dr. Rod Staples: Well, this is a classic multicenter randomized trial performed in the UK. We actually recruited in 17 different UK centers. We asked them to assess patients who were scheduled for invasive, currently angiography for participation against some very minimal inclusion and exclusion criteria, trying to keep the trial generalizable with good external validity. I think one important point to note is that we did allow the inclusion of both patients being assessed with elective angiography for stable symptoms, but in the end half of the population were recruited in the context of a stabilized acute coronary syndrome, a Non-ST-elevation event a day or so down the line. Dr. Greg Hundley: And just a quick breakdown, how many men, how many women? Dr. Rod Staples: Well, it's in that respect, the population is very, very typical for this type of cardiovascular trial. A 70, 30 split an age in the midsixties, a diabetic population in the high teens. So a very typical population we've seen in all this kind of trial environment. Dr. Greg Hundley: Very nice. And so about 1100 patients. And then what were your study results? Dr. Rod Staples: Well, I think there was a very good adherence to the study protocol, very, very few crossovers. And also we were pleased to see that our investigators stayed true to the protocol in that the median number of epicardial vessels assessed by FFR in that randomized arm was four. So there was a good assessment by FFR. The trial was interesting in another respect, in that we assessed an economic outcome based on all NHS hospital costs over the following year and a patient reported outcome based on quality of life using the WHOQOL, and interestingly we found no significant differences either in total subsequent hospital costs from randomization for a year, or indeed in patient reported quality of life by WHOQOL or Angina symptoms by the Canadian Cardiovascular Society classification. Dr. Greg Hundley: Very nice. And then, what about clinical events? Did you examine those as well? Dr. Rod Staples: We did. And again, just a little caveat here, the trial is again interesting in that, what is often in the UK these days called a lean efficient methodology. Whereby, rather than individually contacting individual trial participants or scouring medical records, we interrogated the central national NHS digital repository of all hospital admissions. And we examined electronically a download of every hospitalization event for every patient using algorithms based on diagnostic and procedural codes to define events. And again, we found a very credible representative rate exactly at incidents and events we would've predicted, but again, no difference between the randomized groups. Dr. Greg Hundley: Very nice, well listeners, now we're going to turn to our own Associate Editor, Dr. Nick Mills. And Nick, again, you see many papers come across your desk. What attracted you to this particular manuscript? And it's very interesting study results. Dr. Nick Mills: Thanks, Greg. Firstly, it addresses an important clinical question. Going beyond that, what appealed to me was it was investigator initiated. It was managed by independent trials unit. It recruited a target, it reported the registered outcomes and it was thoughtfully interpreted. And the fact that it didn't prove the hypothesis was irrelevant because it addresses a really important clinical question. And I think it requires some context, and that is that from the previous randomized trials The FAME series, we have been chastised as interventional cardiologists for not using FFR for relatively low use of FFR clinical practice. It's always around one in 20 patients in most series, given the evidence that FFR guided intervention improves outcomes. But actually what FFR is good at is discouraging you from stenting patients with stable Coronary Disease. And so, I think a pragmatic trial that addresses that, the fundamental question, should we be doing more FFR more broadly in both acute and stable disease to guide revascularization with a definitive message that we shouldn't, it doesn't improve quality of life. It doesn't alter costs. Clinical outcomes are similar, but there are more complications associated with routine pressure wire use, gives us a very clear steer for the future. So this is a really important trial addressing a fairly fundamental clinical question. Dr. Greg Hundley: Very interesting. Well, Rod, we're going to turn back to you with Nick's comments and how we're really seeing an evolution in thought processes regarding both diagnostic angiography, and then also the use of functional testing. What do you see is the next study, really in this sphere of research that would be performed? Dr. Rod Staples: Well, I agree with Nick in a way that this raises important philosophical points about the use of intelligence, selective employment of tests or interventions, and that perhaps we need to reflect this in the way we conduct our future studies. I think we're all aware that fractional flow reserve and other measures of functional significance are tremendously valuable in certain clinical settings. And that value's been proven in randomized trials, but in PRECORD 2, for example, if a patient randomized to angiography only was an acute coronary syndrome patient, who had inverted their T waves in their anterior leads, had an associated troponin rise, an echocardiogram had shown some Hypokinesia in the anterior territory. Then I think the potential value of PCI in the LAD does not necessarily require FFR confirmation, and hence that patient will have an equivalent outcome in the angiography group. Similarly, high quality pre-angiography preparation in the elective population with functional testing, stress testing, other forms of imaging mean that we can reserve the use of invasive fractional flow reserve, tight indices to more selective use. Dr. Greg Hundley: And Nick, turning to you, what do you think is the next research study that could be informative in this space? Dr. Nick Mills: I think our whole philosophy by how to manage stable coronary disease is changing. In part because of some other landmark trials that the Ischemia trial and some of the key secondary analyses of the Ischemia trial that tells the Pathoma burden, low attenuation plaque, other aspects of chronic disease are vitally important in predicting major events in the future. And that leaves us with the role for FFR or CT FFR, primarily to manage symptoms. And I think we're getting increasingly good evaluating patients before they get to the Cathflow, optimizing their medical treatment. And so for me, the trial that we really need to help us, is a CT FFR trial to understand the role of Ischemia testing plus anatomical testing and how they dovetail in guiding treatment decisions before they get to the cath lab. I think we need to move this before the lab, always going to be a role for intelligent FFR testing in selected patients once we get to it. But I think that the question probably needs to be addressed before they get to the cath lab. Dr. Greg Hundley: Very nice. Well listeners, we want to thank, Dr. Rod Staples from Liverpool and Dr. Nick Mills from Edinburgh, Scotland for bringing us this very interesting study, highlighting that a strategy of systematic FFR assessment, when compared to angiography alone, did not result in a significant reduction in cost or improvement in quality of life. Well, on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week On the Run. This program is copyright of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

director university uk management scotland trial fame run singapore liverpool richmond lower edinburgh scotland clinical assessing rod nhs southampton cox rna american heart association associate editor lad mace circulation acs agarwal pci decreased angina sglt2 gfr ischemia ldl c apob ripcord ffr empagliflozin vcu health duke national university carolyn lam emperor preserved evolocumab mt1 odyssey outcomes

Recent Clinical Advances in Reducing Risk for Dyslipidemia

Play Episode Listen Later Feb 15, 2022 23:15

In this episode, host Dr. Laurence Sperling speaks with Drs Erin Michos and Peter Toth about optimal use of newer dyslipidemia therapies. Relevant disclosures can be found with the episode show notes on Medscape.com (https://www.medscape.com/viewarticle/958749). The topics and discussions are planned, produced, and reviewed independently of our advertiser. This podcast is intended only for US healthcare professionals. Resources Cholesterol Treatment Trial: Efficacy and Safety of More Intensive Lowering of LDL Cholesterol: A Meta-analysis Of Data From 170,000 Participants in 26 Randomised Trials https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988224/ IMPROVE-IT: Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes https://www.nejm.org/doi/full/10.1056/nejmoa1410489 ODYSSEY: Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome https://www.nejm.org/doi/full/10.1056/nejmoa1801174 FOURIER: Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk -- FOURIER https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2017/03/16/00/46/FOURIER Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.037184 ORION: Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol https://pubmed.ncbi.nlm.nih.gov/32187462/ CLEAR Wisdom: Effect of Bempedoic Acid vs Placebo Added to Maximally Tolerated Statins on Low-Density Lipoprotein Cholesterol in Patients at High Risk for Cardiovascular Disease: The CLEAR Wisdom Randomized Clinical Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865290/ Bempedoic Acid for Heterozygous Familial Hypercholesterolemia: From Bench to Bedside https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121276/ CLEAR Outcomes: Rationale and Design of the CLEAR-Outcomes Trial: Evaluating the Effect of Bempedoic Acid on Cardiovascular Events in Patients With Statin Intolerance https://pubmed.ncbi.nlm.nih.gov/33470195/ CLEAR Wisdom: Bempedoic Acid Plus Ezetimibe Fixed-Dose Combination in Patients With Hypercholesterolemia and High CVD Risk Treated With Maximally Tolerated Statin Therapy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865290/ Bempedoic Acid and Ezetimibe -- Better Together https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203625/ REDUCE-IT: Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia https://www.nejm.org/doi/full/10.1056/nejmoa1812792 STRENGTH: Long-Term Outcomes Study to Assess Statin Residual Risk With Epanova in High Cardiovascular Risk Patients With Hypertriglyceridemia -- STRENGTH https://www.acc.org/latest-in-cardiology/clinical-trials/2020/11/11/21/29/strength JELIS: Effects of Eicosapentaenoic Acid on Major Coronary Events in Hypercholesterolaemic Patients (JELIS): A Randomised Open-Label, Blinded Endpoint Analysis https://pubmed.ncbi.nlm.nih.gov/17398308/ PROMINENT: Rationale and Design of the Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) Study https://pubmed.ncbi.nlm.nih.gov/30342298/ How Low Is Safe? The Frontier of Very Low (< 30 mg/dL) LDL Cholesterol https://pubmed.ncbi.nlm.nih.gov/33463677/ Cholesterol: The Race to the Bottom https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehab446/6335767?searchresult=1 SPARCL: High-Dose Atorvastatin After Stroke or Transient Ischemic Attack https://www.nejm.org/doi/full/10.1056/nejmoa061894 EBBINGHAUS: Cognitive Function in a Randomized Trial of Evolocumab https://www.nejm.org/doi/full/10.1056/nejmoa1701131 PROSPER: Pravastatin in Elderly Individuals at Risk of Vascular Disease (PROSPER): A Randomized Controlled Trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(02)11600-X/fulltext Achievement of Very Low Low-Density Lipoprotein Cholesterol Levels https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.119.044275

Jan 7, 2022 This Week in Cardiology Podcast

This Week in Cardiology

Play Episode Listen Later Jan 7, 2022 20:13

Causes of sudden death, inclisiran, DOAC choices, and alcohol and VT/VF are the topics discussed by John Mandrola, MD, in this week's podcast. To read a partial transcript or to comment, visit: https://www.medscape.com/twic I – Causes of Sudden Death - Cardiac Device Interrogation After Death 'Richly Informative' https://www.medscape.com/viewarticle/965730 - Postmortem Interrogation of Cardiac Implantable Electronic Devices: A 15-Year Experience https://www.jacc.org/doi/full/10.1016/j.jacep.2021.10.011 - Sudden Death in Patients With Cardiac Implantable Electronic Devices https://pubmed.ncbi.nlm.nih.gov/26098676/ - Cardiac Implantable Electronic Device Interrogation at Forensic Autopsy https://www.ahajournals.org/doi/full/10.1161/circulationaha.117.032367 II – Inclisiran - FDA Approves First-in-Class Inclisiran to Lower LDL-C https://www.medscape.com/viewarticle/965464 - ORION: Inclisiran Phase 3 Trials Published https://www.medscape.com/viewarticle/927107 - Meta-Analysis of Inclisiran for the Treatment of Hypercholesterolemia https://pubmed.ncbi.nlm.nih.gov/32892993/ - Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease https://www.nejm.org/doi/full/10.1056/nejmoa1615664 - Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome https://www.nejm.org/doi/10.1056/NEJMoa1801174 III – DOAC Choice - Apixaban: The 'Anticoagulant of Choice' for AF https://www.medscape.com/viewarticle/965390 - Association of Rivaroxaban vs Apixaban With Major Ischemic or Hemorrhagic Events in Patients With Atrial Fibrillation https://jamanetwork.com/journals/jama/fullarticle/2787319 IV – Alcohol and VT/VF and SCD - Some Good News on Alcohol and 'Holiday Heart Syndrome' https://www.medscape.com/viewarticle/965498 - Alcohol consumption and risk of ventricular arrhythmias and sudden cardiac death: An observational study of 408,712 individuals https://www.heartrhythmjournal.com/article/S1547-5271(21)02215-3/fulltext You may also like: Medscape editor-in-chief Eric Topol, MD, and master storyteller and clinician Abraham Verghese, MD, on Medicine and the Machine https://www.medscape.com/features/public/machine The Bob Harrington Show with Stanford University Chair of Medicine, Robert A. Harrington, MD. https://www.medscape.com/author/bob-harrington Questions or feedback, please contact news@medscape.net

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The Clot Thickens: Malcolm Kendrick on the Enduring Mystery of Heart Disease

Nourish Balance Thrive

Play Episode Listen Later Nov 19, 2021 87:51

If you've followed the NBT podcast for a while you probably heard Dr. Malcolm Kendrick talking about the tenuous connection between cholesterol levels and cardiovascular disease. Malcolm has published with The International Network of Cholesterol Skeptics on this topic, including a recent review paper entitled LDL-C does not cause cardiovascular disease. In the paper, they include both total cholesterol and LDL-C in their discussions, and if you look at epidemiological data, I think they make a good point. For instance, total cholesterol had almost no effect on mortality in the HUNT-2 study in Norway, and higher levels were associated with lower mortality risk in women. Or the ESCARVAL-RISK study, where higher LDL-C is associated with lower all-cause mortality until it's well above 200 mg/dl. Or the In-Chianti study, where people over 64 had the lowest mortality rates if they had an LDL-C greater than 130mg/dl. The question then becomes, if not cholesterol, then what? To answer that we must resist monomania and acknowledge the very notion of causation in a complex system is suspicious. Ask not what but how. Malcolm argues in his new book The Clot Thickens that if you maintain metabolic health, manage stress, and mind your endothelial function, cholesterol levels become largely irrelevant. Simple enough, but as you'll discover in this interview, the devil is in the details. Here's the outline of this episode with Malcolm Kendrick: [00:00:24] Previous NBT podcasts with Malcolm Kendrick: Why Cholesterol Levels Have No Effect on Cardiovascular Disease (And Things to Think About Instead) and A Statin Nation: Damaging Millions in a Brave New Post-health World. [00:00:42] Book: The Clot Thickens: The enduring mystery of heart disease, by Malcolm Kendrick. [00:03:04] 5-part series with lipidologist Thomas Dayspring (Part 1, 2, 3, 4, 5); 2-hour interview with Ron Krauss on The Drive Podcast. [00:04:23] Book: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. [00:06:12] LDL Cholesterol - challenging mainstream thought. [00:17:16] Fatty streaks never become atherosclerotic plaques; Review: Velican, C., M. Anghelescu, and D. Velican. "Preliminary study on the natural history of cerebral atherosclerosis." Medicine interne 19.2 (1981): 137-145. [00:18:54] Genetic influences; familial hypercholesterolemia (FH) and high clotting factors; Case study of patient with untreated FH but no presence of atherosclerosis: Johnson, Kipp W., Joel T. Dudley, and Jason R. Bobe. "A 72-year-old patient with longstanding, untreated familial hypercholesterolemia but no coronary artery calcification: a case report." Cureus 10.4 (2018). [00:21:22] Clotting factors more important than high LDL; Paper: Ravnskov, Uffe, et al. "Inborn coagulation factors are more important cardiovascular risk factors than high LDL-cholesterol in familial hypercholesterolemia." Medical hypotheses 121 (2018): 60-63. [00:25:03] UK Biobank Study: Mora, Samia, Seth S. Martin, and Salim S. Virani. "Cholesterol Insights and Controversies From the UK Biobank Study: Three Take-Home Messages for the Busy Clinician." (2019): 553-555. [00:25:51] Machine learning used to predict cardiovascular disease; Study: Weng, Stephen F., et al. "Can machine-learning improve cardiovascular risk prediction using routine clinical data?." PloS one 12.4 (2017): e0174944. [00:30:54] FOURIER PCSK9-inhibitor study: More deaths in the treatment group; Study: Sabatine, Marc S., et al. "Evolocumab and clinical outcomes in patients with cardiovascular disease." New England Journal of Medicine 376.18 (2017): 1713-1722. [00:31:26] Evolocumab also reduces Lp(a); Study: O'Donoghue, Michelle L., et al. "Lipoprotein (a), PCSK9 inhibition, and cardiovascular risk: insights from the FOURIER trial." Circulation 139.12 (2019): 1483-1492. [00:34:02] APOA-1 Milano and HDL cholesterol. [00:38:45] Lp(a) and Vitamin C, plasminogen and clotting. [00:47:02] Rudolf Virchow, the father of the cholesterol hypothesis. [00:48:42] So what causes CVD? [00:49:53] Biomechanical stress; High blood pressure. [00:52:16] Endothelial and glycocalyx damage. [01:02:19] Steroids, immunosuppressants. [01:03:52] Avastin (bevacizumab) increases the risk of CVD; Study: Totzeck, Matthias, Raluca Ileana Mincu, and Tienush Rassaf. "Cardiovascular adverse events in patients with cancer treated with bevacizumab: a meta‐analysis of more than 20 000 patients." Journal of the American Heart Association 6.8 (2017): e006278. [01:06:07] Clotting disorders. [01:10:41] Sickle cell anemia - 50,000% increased risk of CVD. [01:11:36] Case study of 14-year old boy: Study: Elsharawy, M. A., and K. M. Moghazy. "Peripheral arterial lesions in patient with sickle cell disease." EJVES Extra 14.2 (2007): 15-18. [01:13:25] Air pollution, smoking, lead. [01:15:57] Biggest risk factors for CVD. [01:20:09] Supplements that strengthen the glycocalyx; Chondroitin Sulfate. [01:22:12] Malcolm's blog.

Effect of Evolocumab on Complex Coronary Disease Requiring Revascularization

Health Professional Radio - Podcast 454422

Play Episode Listen Later Jan 19, 2021 12:05

Commentary by Dr. Valentin Fuster

disease complex commentary requiring coronary revascularization evolocumab valentin fuster

What does a mainstream cardiologist think of my cholesterol? With Nadir Ali, MD

Paul Saladino MD podcast

Play Episode Listen Later Oct 19, 2020 100:55

Dr. Nadir Ali is an interventional cardiologist with over 25 years of experience. He is also the chairman of the Department of Cardiology at Clear Lake Regional Medical Center. Before working as a cardiologist, he served as an assistant professor of medicine for eight years at Baylor College of Medicine in Houston, where he also received his medical training. Time Stamps: 0:09:44 Podcast Begins 0:11:00 Lifestyle change and the power of animal foods 0:16:38 Is red meat killing us? 0:19:32 Humans are not hebivores 0:24:31 The problem with mainstream cardiology 0:31:03 The full story of LDL [and oxidized LDL] 0:38:22 Changes in Dietary Fat Intake Alter Plasma Levels of Oxidized Low-Density Lipoprotein and Lipoprotein(a) https://www.ahajournals.org/doi/10.1161/01.ATV.0000118012.64932.f4?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed 0:43:23 Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid metabolites in humans https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3467319/ 0:43:50 Strong increase in hydroxy fatty acids derived from linoleic acid in human low density lipoproteins of atherosclerotic patients https://www.sciencedirect.com/science/article/abs/pii/S0009308497000959?via%3Dihub 0:44:44 Linoleic acid is at the root of heart disease 0:50:08 LDL and immune health 0:58:06 Genetic Assessment of Potential Long-Term On-Target Side Effects of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Inhibitors https://www.ahajournals.org/doi/10.1161/CIRCGEN.118.002196 1:00:11 Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease https://www.nejm.org/doi/full/10.1056/nejmoa1615664 1:02:05 Serious adverse events and deaths in PCSK9 inhibitor trials reported on Clinical Trials.gov: a systematic review https://www.tandfonline.com/doi/full/10.1080/17512433.2020.1787832 1:02:56 The dark truth of PCSK9 inhibitors 1:05:12 Metabolic health is what matters 1:07:04 Metabolic health is what matters 1:08:07 Let' change the paradigm! 1:13:21 Dr. Nadir Ali's health optimizaton advice 1:18:12 Where to find Nadir Ali MD 1:22:48 Binding and Partial Inactivation of Staphylococcus aureus a-Toxin by Human Plasma Low-Density Lipoproteinhttps://www.jbc.org/content/258/9/5899.long 1:23:18 Why you should rethink your statin 1:26:24 The Framingham Study 1:26:56 High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study https://www.amjmed.com/article/0002-9343(77)90874-9/pdf 1:28:51 Mechanisms of HDL lowering in insulin resistant, hypertriglyceridemic states: the combined effect of HDL triglyceride enrichment and elevated hepatic lipase activity https://pubmed.ncbi.nlm.nih.gov/12951168/ 1:29:44 LDL size matters 1:31:24 Clinical Effects of Cholesterol Supplementation in Six Patients With the Smith–Lemli–Opitz Syndrome(SLOS) https://www.researchgate.net/publication/14184407_Clinical_effects_of_cholesterol_supplementation_in_six_patients_with_Smith-Lemli-Opitz_syndrome_SLOS 1:32:56 Mood, Personality, and Behavior Changes During Treatment with Statins: A Case Series https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5005588/ 1:34:19 Determination of lipid oxidation products in vegetable oils and marine omega-3 supplementshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3118035/ 1:34:29 Stop your omega-3 supplement! Heart & Soil is my passion based company founded to help a few million more people reclaim their ancestral birthright to radical health through nose to tail nutrition. We are making grass fed, grass finished desiccated organ capsules from regenerative farms in New Zealand and developing a US based supply chain. Check us out at: www.heartandsoil.co, @heartandsoilsupplements on Instagram Belcampo: www.belcampo.com Use the code “carnivoremd” for 20% off your order! BluBlox: www.blublox.com use the code CarnivoreMD for 15% off your order White Oak Pastures: Use the code CARNIVOREMD at www.whiteoakpastures.com for 10% off your first order! Nutrisense: Nutrisense.io

EVACS Trial (Evolocumab in Acute Coronary Syndrome)

Play Episode Listen Later Aug 21, 2020 8:57

Dr. Thorsten Leucker, Assistant Professor of Medicine in the Division of Cardiology, Department of Medicine at the Johns Hopkins University School of Medicine discusses a study, EVACS (Evolocumab in Acute Coronary Syndrome) evaluating a hospital-based intervention option in ACS patients that was published in the American Heart Association’s journal, "Circulation". The study examined LDL-C reduction in non-ST-elevation myocardial infarction (NSTEMI) patients that met certain criteria.

medicine trial assistant professor johns hopkins university american heart association cardiology circulation acs ldl c acute coronary syndrome nstemi evolocumab

25 FOURIER and Evolocumab

Practice Impact Extra

Play Episode Listen Later Jun 30, 2020 3:46

The development of monoclonal antibody PCSK9 inhibitors has allowed for dramatic lowering of LDL and CV events, but what new analysis adds knowledge to the benefits of PCSK9? Dr. Bernie reviews the practice impacting results of a prespecified analysis of FOURIER trial published in JAMA-Cardiology April 2020, to evaluate the LDL cholesterol-lowering effect of Evolocumab on different types and sizes of myocardial infarction.

bernie sanders cv ldl fourier pcsk9 evolocumab

#12 Journal Round Up May '20 : Dementia + AKI + Ammonia + Antiplatlets...+ more!

JournalSpotting.

Play Episode Listen Later Jun 9, 2020 54:27

Here at Journalspotting headquarters we sacrificed our vitamin d levels and frisbee skills during the sunny month of May, and have compiled an episode that will get you up to scratch with what you missed while you were out sunbathing. In this months episode:...Does a lower BP lower the risk of dementia?...(04:38)Hughes, Diarmaid et al. “Association of Blood Pressure Lowering With Incident Dementia or Cognitive Impairment: A Systematic Review and Meta-analysis.” JAMA. doi:10.1001/jama.2020.4249...When's the right time to start dialysis in severe AKI?...(08:51)Gaudry, Stéphane et al. “Delayed versus early initiation of renal replacement therapy for severe acute kidney injury: a systematic review and individual patient data meta-analysis of randomised clinical trials.” Lancet, doi:10.1016/S0140-...Do I really need to find ice for an ammonia level?...(13:10)Haj, Mona, and Don C Rockey. “Ammonia Levels Do Not Guide Clinical Management of Patients With Hepatic Encephalopathy Caused by Cirrhosis.” The American journal of gastroenterology. doi:10.14309/ajg.0000000000000343...Is there a safer antiplatelet for the elderly?...(19:18)Gimbel, Marieke et al. “Clopidogrel versus ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation acute coronary syndrome.” Lancet. doi:10.1016/S0140-6736(20)30325-1...How can we better serve our patients in care homes?...(23:21)Alcorn, Gemma et al. “Care home residents who die in hospital: exploring factors, processes and experiences.” Age and ageing, doi:10.1093/ageing/afz174...Are fancy lipid-lowering drugs all their cracked up to be?...(29:24)Gencer, Baris et al. “Efficacy of Evolocumab on Cardiovascular Outcomes in Patients With Recent Myocardial Infarction: A Prespecified Secondary Analysis From the FOURIER Trial.” JAMA cardiology, doi:10.1001/jamacardio.2020.0882...How significant is the wrong diagnosis?...Newman-Toker, David E et al. “Rate of diagnostic errors and serious misdiagnosis-related harms for major vascular events, infections, and cancers: toward a national incidence estimate using the "Big Three".” Diagnosis (Berlin, Germany), doi:10.1515/dx-2019-0104...Can you trust the EWS score?...Gerry, Stephen et al. “Early warning scores for detecting deterioration in adult hospital patients: systematic review and critical appraisal of methodology.” BMJ. doi:10.1136/bmj.m1501JOURNALBITESCanadian Syncope ScoreOpioids in dialysis patientVTE guideline updatePDE-4 inhibitors and COPD...Cannabis & Fungal Infections...Benedict, Kaitlin et al. “Cannabis Use and Fungal Infections in a Commercially Insured Population.” Emerging infectious diseases. doi:10.3201/eid2606.191570

Evolocumab in HIV-Infected Patients with Dyslipidemia

Play Episode Listen Later May 18, 2020 9:42

Commentary by Dr. Valentin Fuster

patients commentary infected dyslipidemia evolocumab valentin fuster

Cognition after Lowering LDL-Cholesterol with Evolocumab

Play Episode Listen Later May 4, 2020 11:34

Commentary by Dr. Valentin Fuster

commentary lowering cognition ldl cholesterol evolocumab valentin fuster

Long-term Evolocumab in Patients With Familial Hypercholesterolemia: Final Results of the TAUSSIG Study

Play Episode Listen Later Feb 10, 2020 14:16

Commentary by Dr. Valentin Fuster

study patients long term commentary final results taussig familial hypercholesterolemia evolocumab valentin fuster

Evolocumab for Early Reduction of LDL-Cholesterol Levels in Patients with Acute Coronary Syndromes (EVOPACS)

Play Episode Listen Later Nov 12, 2019 13:43

Commentary by Dr. Valentin Fuster

patients syndrome levels commentary reduction acute coronary ldl cholesterol evolocumab valentin fuster

Long-term Efficacy and Safety of Evolocumab in Patients with Hypercholesterolemia

Play Episode Listen Later Oct 21, 2019 12:13

Commentary by Dr. Valentin Fuster

safety patients long term commentary efficacy evolocumab valentin fuster

A Statin Nation: Damaging Millions in a Brave New Post-health World

Nourish Balance Thrive

Play Episode Listen Later Sep 2, 2019 142:55

Scottish doctor, writer, speaker, and outspoken cholesterol sceptic Malcolm Kendrick is back on the podcast this week. He continues to challenge the widespread use of statin medications, despite being targeted personally and professionally by those opposing his message. Since we last talked he has authored a new book, A Statin Nation: Damaging Millions in a Brave New Post-health World, elucidating his position against mainstream medicine’s rampant cholesterol-lowering tactics. On this podcast, Dr. Kendrick describes in detail exactly what he believes drives the process of cardiovascular disease, informed from 35 years of research on the subject. He explains specifically why cholesterol has been misunderstood, and how medicine got it wrong. We discuss corruption in medical research and the money supporting the status quo, and Dr. Kendrick shares some of the best ways to avoid heart disease (which have little to do with diet!). Here’s the outline of this interview with Malcolm Kendrick: [00:00:07] Our first podcast with Malcolm Kendrick: Why Cholesterol Levels Have No Effect on Cardiovascular Disease (And Things to Think about Instead). [00:00:30] Book: A Statin Nation: Damaging Millions in a Brave New Post-health World, by Dr. Malcolm Kendrick. His previous two books: Doctoring Data and The Cholesterol Con. [00:02:00] Causes vs processes. [00:03:40] History behind his journey and questioning authority. [00:07:30] Articles written by Elspeth Smith. [00:09:00] Karl Rokitansky’s paper discussing an alternative way of looking at CVD: A manual of pathological anatomy, Vol. 4. Day GE, trans. London: Sydenham Society, 1852:261; in print here. [00:09:06] Rudolf Virchow, researcher who pointed to cholesterol in artery walls. [00:10:55] Researcher Nikolai N. Anichkov: fed rabbits a high-cholesterol diet and cholesterol appeared in their arteries (sort of). [00:12:07] Ancel Keys; blaming saturated fat. [00:14:11] France - highest saturated fat consumption, lowest rate of CVD. Georgia - lowest sat fat consumption, highest rate of CVD. See graph, here. [00:15:16] International Network of Cholesterol Skeptics (THINCS). Study: Ravnskov, Uffe, et al. "Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review." BMJ open 6.6 (2016): e010401. [00:16:50] Pleiotropic effects of statins. [00:17:29] Movie: 12 Angry Men (1957). [00:20:30] Robert Ross - response to injury hypothesis; Study: Ross, Russell, John Glomset, and Laurence Harker. "Response to injury and atherogenesis." The American journal of pathology 86.3 (1977): 675. [00:20:40] TV show: Stranger Things. [00:22:31] Infectious disease hypothesis. [00:22:52] Analogy of rust in the paint of a car; Sickle Cell Disease as an example. [00:27:12] 14-year old boy with Sickle Cell and atherosclerosis; Study: Elsharawy, M. A., and K. M. Moghazy. "Peripheral arterial lesions in patient with sickle cell disease." EJVES Extra 14.2 (2007): 15-18. [00:28:57] Endothelial progenitor cells, produced in the bone marrow, discovered in 1997. [00:29:31] Pig study of endothelial turnover: Caplan, Bernard A., and Colin J. Schwartz. "Increased endothelial cell turnover in areas of in vivo Evans Blue uptake in the pig aorta." Atherosclerosis 17.3 (1973): 401-417. [00:31:48] Vitamin C's role in maintaining collagen and blood vessels. [00:33:08] Lp(a) molecules - patching cracks in the artery walls. [00:33:42] Depriving guinea pigs of vitamin C caused atherosclerosis; Study: Willis, G. C. "The reversibility of atherosclerosis." Canadian Medical Association Journal 77.2 (1957): 106. [00:34:24] Linus Pauling - said CVD was caused by chronic low-level vitamin C deficiency. [00:35:53] What else damages endothelial cells? Many things, including smoking, air pollution, high blood sugar, Kawasaki disease, sepsis/infection. [00:41:19] Glycocalyx; Nitric oxide. [00:43:30] Health benefits of sun exposure. [00:44:26] Biomechanical stress (blood pressure) - atherosclerosis in arteries but not in veins. [00:47:57] Things that interfere with repair: steroids, vascular endothelial growth factor (VEGF) inhibitors. [00:55:00] The effects of stress on the cardiovascular system. [00:57:55] Red blood cells are what brings cholesterol into blood clots. [00:58:59] Cholesterol crystals in atherosclerotic plaques come from red blood cells. Study: Kolodgie, Frank D., et al. "Intraplaque hemorrhage and progression of coronary atheroma." New England Journal of Medicine 349.24 (2003): 2316-2325. [01:00:55] Very low-density lipoproteins (VLDLs) are procoagulant; High-density lipoprotein (HDL) is anticoagulant. [01:03:46] Familial hypercholesterolemia (FH); Factor VIII. [01:08:15] Cholesterol-lowering pharmaceuticals; Repatha. In the clinical trial, the total number of cardiovascular deaths was greater in the Repatha group than the placebo group. Study: Sabatine, Marc S., et al. "Evolocumab and clinical outcomes in patients with cardiovascular disease." New England Journal of Medicine 376.18 (2017): 1713-1722. [01:09:34] David Deamer, biologist and Research Professor of Biomolecular Engineering. [01:10:05] Karl Popper, philosopher. [01:10:28] Bradford Hill’s Criteria for Causation. [01:13:52] Michael Mosley, BBC journalist. [01:16:40] Statin denialism - an internet cult with deadly consequences? [01:19:18] The money behind the statin and low-fat industries. [01:20:06] Margarine; Trans-fatty acids, banned in several countries. [01:24:37] The impact of food; The focus on food to the exclusion of other pillars of health. [01:26:38] Dr. Phil Hammond; CLANGERS [01:28:21] Avoiding internet attacks. [01:32:00] ApoA-1 Milano. Original study: Nissen, Steven E., et al. "Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial." Jama 290.17 (2003): 2292-2300. [01:33:05] The Heart Protection (HPS) Study in the UK: Heart Protection Study Collaborative Group. "MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo controlled trial." The Lancet 360.9326 (2002): 7-22. [01:33:36] Scandinavian Simvastatin Survival Study (4S) Scandinavian Simvastatin Survival Study Group. "Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)." The Lancet 344.8934 (1994): 1383-1389. [01:33:49] West of Scotland Coronary Prevention Study (WOSCOPS): Shepherd, James, et al. "Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia." New England Journal of Medicine 333.20 (1995): 1301-1308. [01:34:21] National Institute of Health’s ALLHAT-LLT trial: Officers, A. L. L. H. A. T. "Coordinators for the ALLHAT Collaborative Research Group: Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs. usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT)." JAMA 288.23 (2002): 2998-3007. [01:34:50] 2005 - Regulations guiding clinical trials changed. [01:35:14] Negative antidepressant studies not published; Study: Turner, Erick H., et al. "Selective publication of antidepressant trials and its influence on apparent efficacy." New England Journal of Medicine 358.3 (2008): 252-260. [01:37:11] Minnesota Coronary Experiment (MCE): Analysis of recovered data: Ramsden, Christopher E., et al. "Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73)." bmj 353 (2016): i1246. [01:39:44] Why Most Published Research Findings Are False: Ioannidis, John PA. "Why most published research findings are false." PLoS medicine 2.8 (2005): e124. [01:39:55] Richard Horton, editor of the Lancet: half of what is published is not true: Horton, Richard. "Offline: What is medicine’s 5 sigma." Lancet 385.9976 (2015): 1380. [01:41:11] The problem with reproducibility; a database of clinical trials that cannot be challenged or reproduced. [01:42:37] Editors of prominent journals losing faith in published research: Marci Angell, Richard Smith [01:44:55] Parachute study: Yeh, Robert W., et al. "Parachute use to prevent death and major trauma when jumping from aircraft: randomized controlled trial." bmj 363 (2018): k5094. [01:46:01] Benefits that are major are obvious; no randomized clinical trial necessary. [01:48:33] Preventing vs. screening. [01:51:42] Podcast: Movement Analysis and Breathing Strategies for Pain Relief and Improved Performance with physical therapist Zac Cupples. [01:51:59] Analysis of women who died in various ways, examining breast tissue; found that a high % of women had what you could diagnose as breast cancer. Study: Bhathal, P. S., et al. "Frequency of benign and malignant breast lesions in 207 consecutive autopsies in Australian women." British journal of cancer 51.2 (1985): 271. [01:53:34] Screening programs not associated with reduced CVD or death; Study: Krogsbøll, Lasse T., et al. "General health checks in adults for reducing morbidity and mortality from disease: Cochrane systematic review and meta-analysis." Bmj 345 (2012): e7191. [01:54:26] Coronary Artery Calcium (CAC) scan. Podcast: Coronary Artery Calcium (CAC): A Direct Measure of Cardiovascular Disease Risk, with Ivor Cummins. [01:54:46] Cardiologist Bernard Lown. [01:58:38] People who had measles/mumps less likely to get CVD; Study: Kubota, Yasuhiko, et al. "Association of measles and mumps with cardiovascular disease: The Japan Collaborative Cohort (JACC) study." Atherosclerosis 241.2 (2015): 682-686. [02:00:55] Life expectancy in US and UK is now falling. [02:06:46] Physical health doesn't exist without social health and psychological health. [02:07:40] Negative Twitter messages correlate with rates of heart disease; Study: Eichstaedt, Johannes C., et al. "Psychological language on Twitter predicts county-level heart disease mortality." Psychological science 26.2 (2015): 159-169. [02:09:58] People who take statins believe they’re protected so they stop exercising. Study: Lee, David SH, et al. "Statins and physical activity in older men: the osteoporotic fractures in men study." JAMA internal medicine 174.8 (2014): 1263-1270. [02:11:45] Simple changes: make friends, have good relationships, speak to your kids, exercise, eat natural food, sunshine. [02:16:53] Blood sugar measurements following funny lecture vs. boring lecture; Study: Hayashi, Keiko, et al. "Laughter lowered the increase in postprandial blood glucose." Diabetes care 26.5 (2003): 1651-1652. [02:18:08] Dr. Malcolm Kendrick’s blog.

tv american history world health movies uk france british west benefits blood simple australian medicine bbc original lack negative millions scottish stranger things trans prevention diabetes laughter vol analysis coordinators preventing psychological national institutes increased frequency lp regulations screenings schwartz milano pig officers editors criteria horton vitamin c cholesterol selective lancet jama parachutes infectious damaging analogy new england journal pain relief cochrane familial kawasaki peripheral research professor hdl angry men bmj keiko sickle cell caplan statins causation sickle cell disease cvd fh brave new richard smith karl popper nissen yeh margarine statin robert w atherosclerosis marcs international network new post michael mosley plos vegf nitric uffe biomechanical ramsden steven e depriving ancel keys randomised linus pauling endothelial robert ross ivor cummins biomolecular engineering frank d improved performance canadian medical association journal clangers glycocalyx richard horton antihypertensive factor viii rudolf virchow bradford hill evolocumab repatha david deamer evans blue johannes c

Efficacy and Safety of Evolocumab in Chronic Kidney Disease: Data from the FOURIER Trial

Gesünder mit praktischer Medizin

Play Episode Listen Later Jun 10, 2019 12:27

Commentary by Dr. Valentin Fuster

data safety trial commentary efficacy chronic kidney disease fourier evolocumab valentin fuster

#24 Cholesterin und Fett: Was wir wirklich wissen

Play Episode Listen Later May 5, 2019 26:19

Heute geht es innerhalb einer kleinen Serie zu Ernährung um das Thema Cholesterin. // Cholesterin? // Lipoproteine Low densitiy, niedrige Dichte Gut / schlecht Hohe dichte, korreliert nur Nüchtern Die neue Leitlinie fordert nicht nüchtern zu sein für Lipidprofil LDL-C ist ausreichend, sofern die Triglyceride nicht über 400 mg / dl liegen. // Cholesterin-reduzierte Diät // Ca. 30.000 Erwachsenen USA mittlere Nachbeobachtungszeit von 17,5 Jahren // Höherer Konsum von Eiern und anderem Cholesterin (Fleisch) korreliert mit HKL-Erkrankung und Sterblichkeit, Dosis-Wirkungs-Beziehung. // Einschränkungen: // Zusammenhang zwischen Eierkonsum/Cholesterin mit Plasmalipiden und Lipoproteinen nicht untersucht, nur vermutet LDL Es existieren aber Studien bei denen alle Bestandteile der Diät außer Cholesterin kontrolliert wurden, dort steigende LDL-C: Ginsberg et al. Arterioscler Thromb. 1994;14(4):576-586; Ginsberg et al. Arterioscler Thromb Vasc Biol. 1995;15(2):169-178. Aber nicht immer: Nicht immer: Blesso & Fernandez Nutrients. 2018; 10(4):E426. Beobachtungstudie, keine gezielte Intervention mit Kontrolle, nur Korrelation, keine Ursachen-Wirkungsbeziehung, Nur für sehr hoher Ei-Verzehr 2-4 Eier pro Tag deutlich (ähnlich Salz-Studien…) // Demgegenüber // Gewichtsverlust / Diät // Ob Fett- oder Kohlehydrat-reduzierte Diät, egal, innerhalb 12 Monaten -> Nochmal separat Diäten... // doi:10.1001/jama.2018.0245 // Fett-Ersatz/Austauschstoffe // ErsatzPhysikalischen Eigenschaften von Fett, chemisch keine Ähnlichkeit mit natürlichen Fetten. Zucker mit anderen Kohlenhydraten und Fettsäuren und Paraffinen (Erdöl / Braunkohle) Olestra seit den 1990er-Jahren zugelassen, nicht EU. kein Brennwert, unverdaulich, unverwertet wieder ausgeschieden: Kartoffelchips und andere Snacks. // AustauschIn der EU zugelassen. Natürliche Ausgangsprodukte, Kohlenhydraten oder Eiweiß. Vor allem in Light-Produkten, um den Fettgehalt und Brennwert zu reduzieren. Nur begrenzt erhitzen, da Eiweiß nur bis etwa 65°C hitzestabil. In Süßspeisen, Eiscreme oder Mayonnaise. Carrageen, Inulin, Maltrin: Kohlenhydrat bzw. Stärke Simplesse: Eiweiß // Beides pervers: Ungesunde Fehlernährung wird zum Schein korrigiert Hände weg / Löffel weg von solchen prozessierten Kunstprodukten // Cholesterin-Senker Statin Ezetimib - HDL - Ionenaustauschharze - Antientzündlich Cantos HKL gesenkt DOI: 10.1056/NEJMoa1707914 => Statin-Therapie // Durch die pharmakologische Senkung des LDL-C werden die ASCVD-Ereignisse (Myokardinfarkt, Schlaganfall und kardiovaskulärer Tod) reduziert. // Das Prinzip, dass eine niedrigere LDL-C-Dosis besser ist, wurde durch neue Studien bestätigt Ezetimib oder Proprotein-Convertase-Subtilisin / Kexin Typ 9 (PCSK9)-Hemmer zu einer Statin-Therapie addiert wurden. // Sekundärprävention= Wenn klinische Symptome, // LDL-C um mehr als 50% reduzieren, Statine hoher Intensität Atorvastatin ≥ 40 mg / d oder Rosuvastatin ≥ 20 mg / dl Bei sehr hohem Risiko (Abbildung) LDL-C auf weniger als 70 mg / dl Ezetimib und gegebenenfalls einen PCSK9-Inhibitor, Alirocumab und Evolocumab. // Primärprävention = Noch keine Symptome, aber LDL-C ≥ 190 mg/dL geringere vaskuläre Ereignisse mit Statinen, nicht jedoch Ezetimib.40-75 JDiabetes + LDL-C von 70 mg / dl Statin-Therapie mit mittlerer Intensität.HKL-Risiko berechnet niedriges Risiko über einen Zeitraum von 10 Jahren weniger als 5% bezeichnet mittel 7,5% bis 19,9% Reduktion um mehr als 30% hoch 20% oder höher ie bei Patienten mit Symptomen: LDL-C-Reduktion von mehr als 50% einleiten; // doi:10.1001/jama.2019.0015 // WissenslückenPersonen im Alter von 20 bis 40 Jahren ≥ 160 mg / dL + Familienanamnese + hohen HKL-Risiko; aber epidemiologische Studien Anza...

european union noch snacks serie wissen nur tod monaten intervention wirklich ern kontrolle ereignisse risiko studien zucker konsum patienten fett ins symptome eier zeitraum mayonnaise schein intensit nochmal ginsberg bestandteile reduktion schlaganfall eiwei eiern senkung fetts sterblichkeit korrelation cholesterin fetten kohlenhydraten ldl c leitlinie eiscreme triglyceride kartoffelchips inulin statine fettgehalt evolocumab light produkten statinen brennwert dosis wirkungsbeziehung alirocumab lipoproteinen

Pharmapills puntata n.84. Aifa apre la consultazione sui trial di farmaci e dispositivi medici

Play Episode Listen Later Mar 20, 2019 10:22

PharmaPills - Pillole dal farmaceutico: Novità, Curiosità e Lavoro dal mondo del farmaceutico. A cura di Stefano Lagravinese.In questa puntata parliamo di:Novo Nordisk, Molmed, Aifa, HIV-1, Evolocumab e Pembrolizumab.Aziende: Novo Nordisk, Molmed, Rocket Pharma, AIFA, SyneosHealth.Persone: Stefano Merizzoli (Novo Nordisk Italia), Luca Alberici (Molmed), Alberto Zambon (Università di Padova), Luis Paz-Ares (Ospedale Universitario “Doce de Octubre”).Nuove terapie: GS-6207, Evolocumab, Pembrolizumab.Patologie: HIV-1, ipercolesterolemia, tumore al polmone.Lavoro: CRA II Sponsor dedicato, Medical Science Liaison (home-based), Clinical Research Associate Free-lance.Il mercoledì alle h 12.00 su Spreaker.com e iTunes.Seguici su: www.telegram.me/pharmapillswww.facebook.com/pharmapills/

trial hiv spreaker lavoro medici gs nuove novo nordisk cra scienza novit padova curiosit apre seguici aifa farmaci medical science liaison pembrolizumab dispositivi evolocumab

Pharmapills puntata n.84. Aifa apre la consultazione sui trial di farmaci e dispositivi medici

Play Episode Listen Later Mar 20, 2019 10:22

trial hiv spreaker lavoro medici gs nuove novo nordisk cra scienza novit padova curiosit apre seguici aifa farmaci medical science liaison pembrolizumab dispositivi evolocumab

Circulation March 19, 2019 Issue

Play Episode Listen Later Mar 18, 2019 23:32

Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to The Journal and it's editors. We're your co-hosts. I'm Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley: And I'm Greg Hundley, also Associate Editor from the Pauley Heart Center in Richmond, Virginia, VCU Health Sciences. Dr Carolyn Lam: How well are we doing with guideline-directed stroke prevention therapy in atrial fibrillation? Well, there are going to be very important results that you need to hear about from Get With the Guidelines Atrial Fibrillation. That's our feature paper coming right up in a future discussion. But first, you've got Greg and I discussing really important papers that we've spotted in The Journal. Greg. Dr Greg Hundley: Absolutely, Carolyn. And my favorite kind of follows from that 'cause it's really about left atrial electromechanical remodeling following two years of high intensity exercise training in sedentary middle-aged adults, kind of like me. The studies from Ben Levine at University of Texas Southwestern Medical Center in Dallas. So, what he's driving at here are moderate-intensity exercises associated with a decrease in incidents of atrial fibrillation. However, extensive training in competitive athletes is associated with an increased atrial fibrillation risk. So, in this study, they're looking at the effects of 24 months of high-intensity exercise training on left atrial mechanical as well as electrical remodeling in sedentary, healthy, middle-aged adults. So, he had 61 individuals, their average age was 53.5 years, quite young, who were randomized to 10 months of exercise training followed by 14 months of maintenance exercise and some stretching or stretching and balance control. He also had another group of 14 master's athletes that were added for a comparison and he looked at three of the echocardiograms to assess left atrial and left ventricular volumes and also had signal average EKG's for filtered P-wave durations and atrial light potentials. He made assessments at baseline, so before everyone started, and 10 and 24 months. Dr Carolyn Lam: Hold on, hold on. Let's really understand here how much exercise were these sedentary middle-aged adults subjected to. Dr Greg Hundley: So, let's talk about that because that was very interesting because a lot of us are out there exercising. So briefly the way he started this, there was an initial phase that was comprised of six months of regressive training during which an increase in the frequency, the duration, and the intensity of exercise, including two high-intensity aerobic interval sessions per week that were prescribed to peak training load. The peak training load included five to six hours of exercise per week that included two interval sessions, at least one being an hour-long session, and then two 30-minute sessions. Once you got that peak training load, that was sustained for four months and then he made these 10-month measurements as part of his study design. Now following that phase, a 14-month sort of a continuation, all of the 24 months, a 14-month period of maintenance exercise was completed where the frequency of high-intensity intervals was reduced to once per week plus continuous training all the way to that 24-month time point. And during the maintenance phase, participants performed a total of about three hours a week of aerobic exercise. Dr Carolyn Lam: Well, don't keep us in suspense now. What did the study show? Dr Greg Hundley: So at the 24 month time point of high-intensity exercise, it led to a disproportionate dilation of the left atrium compared to the left ventricle. So, mechanical changes, but no electrical remodeling was seen. And interesting, and remember he had that comparison cohort with master's athletes. Those participants randomized exercise training demonstrated lower absolute left atrial and left ventricular volumes, but a similar left atrial to left ventricular ratio after 24 months of exercise training. So, what's going on here, if you're middle-aged or young, some of us like to think, and you start one of these aggressive training sessions, you do have some changes mechanically in the shaping of your left atrium and left ventricle, but they're concordant, but no electrical remodeling that was observed in this situation. So, how do those elite athletes develop atrial fibrillation in the electrical remodeling? Don't know. It may be they need a longer duration of exercise. Maybe they start at a different time point because these are relatively sedentary individuals, and maybe their training regimen is very different. So, more research is needed, but it was interesting that these middle-aged folks that start with this little bit more aggressive regimen really didn't develop the electrical remodeling. So, Carolyn, you've got a couple of papers that are sort of tied together. Dr Carolyn Lam: Indeed. A couple of papers centered on lipoprotein little A. Now, we know that lipoprotein little A levels predict the risk of myocardial infarction and this has been shown in populations of European ancestry, however there's very little data available in other ethnic groups. And so, this was addressed by Dr Paré from McMaster University and the Interheart Investigators who looked at more than 6000 cases of first myocardial infarction and more than 6800 controls, all from the Interheart study, and were stratified by ethnicity and included African, American, Chinese, European, Latin American, South Asian, and Southeast Asian ancestries. Lipoprotein little A concentration was measured in each participant, first using an SA that was insensitive to iso-form size and then iso-form size itself was also assessed by Western Blot in a subset of more than 4200 participants. So, what they found was that lipoprotein little A concentration and iso-form size varied markedly among the ethnic groups. Africans had the highest concentrations with the smallest iso-form size whereas Chinese had the lowest concentrations with the largest iso-form size. Furthermore, higher lipoprotein little A concentrations were associated with an increased risk of myocardial infarction and carried an especially high population burden in South Asians and Latin Americans. And a high concentration above 15 milligrams per deciliter was associated with significantly increased risk of myocardial infarction in all populations except Arabs and Africans. The iso-form size, on the other hand, was inversely associated with lipoprotein little A concentrations and did not significantly contribute to the risk. Dr Greg Hundley: So, Carolyn, how do we use this clinically? I mean, do we measure this in folks? Dr Carolyn Lam: Yeah. So, there are two take-home messages. I think one is about the monitoring or measuring and it supports a clinical use of the actual lipoprotein A concentration rather than iso-form size as a marker of myocardial infarction in this ethnically diverse population. But this is, other than Africans and Arabs where, remember that cut off did not seem to associate with a risk of MI's in these two ethnicities. The second take-home is that the effects of clinical interventions that reduce lipoprotein A should be investigated especially in South Asians and Latin Americans where the population attributable risk is really high. And that actually brings me to the second study. So, we've always been looking for intervention that can reduce lipoprotein A and this current paper is really interesting 'cause it talks about insights from the Fourier trial. So, we may finally have a therapy that can reduce it. Dr O'Donoghue from the TIMI study group and Brigham and Women's Hospital in Boston, Massachusetts and colleagues looked at the relationship between lipoprotein A levels, PCSK9 inhibition, and cardiovascular risk in the Fourier trial, which you remember is a randomized trial of Evolocumab versus placebo in patients with established atherosclerotic cardiovascular disease. So, they found that patients with a higher concentration of lipoprotein little A were at increased risk of coronary events independent of the LDL concentration. And individuals with a higher baseline LP little A concentration tended to have a greater relative and absolute coronary risk reduction with Evolocumab and therefore a lower number needed to treat. It was as low as four T for individuals with a lipoprotein A above the median versus 105 number needed to treat for those at or below a lipoprotein A level below the median. Dr Greg Hundley: So should we start checking this in all our patients now, these lipoprotein little A levels? Dr Carolyn Lam: Yeah. So, this issue was discussed beautifully in a company editorial by Dr Thanassoulis from McGill University Health Center. And here he mentions that there remains tremendous clinical inertia honestly for the measurement of lipoprotein A in North America and in fact, worldwide. For this to be successful, we really need to be proactively screening our patients with myocardial infarction and stroke and especially those with premature events or a family history. And particular attention will need to be made on screening individuals with recurrent events despite adequate lipid or LDL lowering who frequently may still have high lipoprotein little A. It's encouraging to know that the most recent version of the US Lipid Guidelines has newly recommended LP little A measurements in select individuals as a risk enhancer and so this should further raise awareness of lipoprotein little A as a risk marker. Finally, the editorialist mentioned that common misconception that we have a lack of therapeutic options to lower high LP little A. Still, we need to remember that these individuals may obtain significant benefit from more aggressive lifestyle modifications. And now we have these results of this trial that suggest that PCSK9 may be one of the few drugs that can lower lipoprotein little A. And so, the editorialist actually ended with targeting therapy for lipoprotein A is around the corner and a test of this hypothesis is really imminent, so we should watch this space. Dr Greg Hundley: Yeah, so it sounds like another wonderment of PCSK9 inhibitors. Dr Carolyn Lam: Yeah. Dr Greg Hundley: Well Carolyn, let me jump in and finish our chat here talking about iron. This particular paper is from Dr Jean-Sébastien Silvestre from Paris, France, and he's looking at the iron regulator Hepcidin. So, we know that iron deficiency is frequent in patients with coronary artery disease and increases morbidity in those with high risk profiles such as those with diabetes and anemia and then conversely, excess iron is also detrimental to cardiac function. We see this with iron overload cardiomyopathies and as a major co-morbidity in patients with genetic hemochromatosis. So, among the multiple regulators of iron homeostasis is Hepcidin. It plays an instrumental role in fine-tuning systemic iron trafficking by modulating the transfer of dietary, recycled, and stored iron from intracellular compartments to extracellular fluids. Hepcidin is a catatonic peptide hormone. It's produced primarily by hepatocytes, but also, it's produced in macrophages. So, given the role of Hepcidin to locally regulate cardiac function and that inflammation guides cardiac remodeling after acute MI, the investigators hypothesized that inflammatory macrophages may control cardiac repair through a Hepcidin-dependent mechanism. And until now, the role of Hepcidin in some other cardiac diseases challenged by inflammation hasn't really been explored. Dr Carolyn Lam: Huh, interesting. So, what did they find? Dr Greg Hundley: Great question and let's lead to the main results of this study. The hormone Hepcidin, they found, was produced by a distinct sub-population of inflammatory cardiac macrophages residing in infarcted heart tissue and the deletion of Hepcidin in macrophages improved tissue remodeling and stimulated cardiomyocyte renewal in both, just as our wonderful basic science studies have, in both adult mice with myocardial infarction, neonatal animals with apical resection and also in human subjects. And so, this study provided novel insights into the complex roles of the immune response during cardiac repair following MI and suggests and deleterious role for the macrophage-derived Hepcidin in cardiac repair. Interesting, Carolyn. Another role for iron in acute MI and more research to come. Dr Carolyn Lam: Indeed. Well, thanks Greg. Let's move on to our feature discussion, shall we? For our feature discussion today, we are talking about the first results from the Get With the Guidelines atrial fibrillation. That is huge, and I have none other than the first author, Dr Jonathan Piccini from Duke Clinical Research Institute, as well as Dr William Lewis from Case Western Reserve University here to discuss these really important results, so listen up. I think to start with it is such an honor to have you with us, Bill. I mean, as Chair of the Get With the Guidelines atrial fibrillation work group, could you give us a background on how did this start? How far has it come? Dr William Lewis: The Get With the Guidelines program started in 2000. Greg Fonarow figured out that if we put in place mechanisms to improve adherence, that we could get people on appropriate therapies. In 2012, there was some focus on atrial fibrillation and I had been participating in the program since 2004 and I kept telling them that A-fib was a big, big problem. And in 2012, they said, "Let's do this," so we built this program to try to improve adherence in atrial fibrillation. Get With the Guidelines is a national, hospital-based, quality improvement program that improves adherence to guidelines over time and it has been very successful at doing that. So, by 2013 we were ready to start enrolling patients and we started getting patients in the database and we're now up to about 162 hospitals nationwide, in the United States, and we've enrolled about 75000 patients in the program. So, it's been very successful from that standpoint. Dr Carolyn Lam: Congratulation. And today we're actually going to be talking about that very question you asked. Adherence. How well are we adhering to guideline-directed stroke prevention therapy for atrial fibrillation? Jonathan, wanna share the key results? Dr Jonathan Piccini: I think you're getting exactly to the point of what was the rationale for this study and I think most individuals that are familiar with the field and atrial fibrillation and also clinicians across the world who are treating patients with atrial fibrillation know that most large reports, most nationwide studies have shown that adherence for oral anticoagulation to prevent stroke in patients with atrial fibrillation usually ranges in the 50, 60, 70 percent range at best. And there's been some notable publications in the past several years from nationwide registries that have shown rates as low as 50 percent or lower in high-risk patients. So, one of the main goals of the program, as Bill articulated, was to try and improve the use of oral anticoagulation in patients who had a guideline recommendation. So, patients who had a CHA2DS2-VASc score of two and higher with atrial fibrillation. And so, looking at over 30000 admissions between 2013 and 2017 and the guidelines A-fib program, we saw that just under 60 percent of patients who had known AF at the time of admission were on oral anticoagulation. And not surprisingly, the patients who were on oral anticoagulation had lower rates of stroke during their hospitalization. But the major finding from the program was that in this quality improvement program, the program was able to improve adherence to oral anticoagulation at discharge from 60 percent to admission all the way up to 93.5 percent in the overall cohort. And if you looked at results over time, adherence improved from 80 percent at discharge all the way to 96 percent and those improvements were sustained in follow up as well. Dr Carolyn Lam: Could you tell us, what do you think are the key elements that help this improvement? Is it just because there's a program and people know they're being watched? Is it that there was a change? I mean, when you say oral anticoagulants I bet you mean both Warfarin and the newer oral anticoagulants, so how much did that help? What do you think is the key ingredient here? Dr Jonathan Piccini: It was several things. Having visited several of these hospitals and spoken with them about the impact of the program, I think you can't emphasize enough that if you don't measure something, you can't really expect to improve it. So, just the fact that hospitals were having systematic data on their atrial fibrillation patients at discharge illustrating who was and who was not getting oral anticoagulation makes a big difference. Between the program itself and the conferences affiliated with the program and teaching sessions affiliated with the program, there's a heavy emphasis on education of the importance of guideline recommended treatments for atrial fibrillation, so that's a second component. And then there's an iterative relationship between the sites and the American Heart Association where improvements in the rates of oral anticoagulation are recognized and celebrated. And I think it's not any one thing, in my opinion. I think it's all of those things taken together. And again, Bill, who's been with the program since its inception probably has additional thoughts on that as well. Dr Carolyn Lam: Bill, did you expect such remarkable results? Dr William Lewis: No. I actually didn't expect 96, but in a previous study where we were looking at patients who had had a stroke in the stroke database, we were able to achieve 93 percent adherence. And so, 96 is remarkable and it's the highest number that's ever been seen in any A-fib program. I was going to mention about the idea of what makes the special sauce, if you will, and I think John put forth a number of items. I think, again, celebrating success, those kinds of things, but I think that docs, by their very nature, are very competitive and when you get a data report that says you're doing x percent and somebody else is doing y percent and their percentage is higher, you tend to get motivated to actually do better. And so, we provide these reports in the program to hospitals so that they can measure their success against other institutions. Dr Carolyn Lam: That's such a good idea. And, you know, I practice here in Asia and there aren't these very massive programs that are accepted in many places. So, what do you think is the generalizability of something like this? Dr Jonathan Piccini: That's such a critical question because a limitation is that these are hospitals that are saying voluntarily, "We want to commit to the program because we think quality care for atrial fibrillation patients is important." And so, you could argue that, well, these results really don't generalize to your run of the mill hospital in different parts of the world. And I think while that's a limitation, it's also a call for what the next steps are. So, having visited many of these hospitals, these are real hospitals of brick and mortar that face many of the same challenges other health systems and hospitals across the world do and I think the key message is that a hospital that implements these types of interventions is very likely to see the same improvement with their patients. And so, I think that's a very important message and a very positive message for patients all over the US and all over the world. Dr William Lewis: I agree. I think it's, not turn-key, it's much more generalizable than we had ever expected. So, community hospitals do this. The American Heart Association is using other Get With the Guidelines programs in China. I think that there is a lot that has to do with the support that's provided by the program and the tools that are made available to them to be able to make it so that you can recreate it in a hospital. I agree, it is more difficult in some hospitals than others. Dr Carolyn Lam: John, before we end, what are the take-home messages for clinicians listening out there? Dr Jonathan Piccini: I'd have two messages. The first message is that this study shows that with some assistance any healthcare system or hospital can achieve optimal adherence to these medications for their patients and thus in so doing achieve a significant benefit for the public health. And the second message I would have, which isn't necessarily specifically related to the paper, but I think it's equally important, that this is just the beginning for the American Heart Association and the Heart Rhythm Society Get With the Guidelines A-fib registry. Though stroke prevention is obviously just one of many different aspects of quality care for atrial fibrillation and so keep an eye out 'cause you'll be seeing a lot of studies coming out about how Get With the Guidelines A-fib is better informing care and treatment for atrial fibrillation across many different therapy domains, including catheter ablation and rate control and other interventions for rhythm control. And again, on behalf of all the co-authors and the American Heart Association, the Heart Rhythm Society sponsors, we really appreciate to have the opportunity to talk about the program. Dr Carolyn Lam: Thank you so much for sharing that with us. Audience, you heard it right here on Circulation on the Run. Don't forget to tune in again next week. This program is copyright American Heart Association 2019.

Evolocumab and Coronary Plaque Composition

Play Episode Listen Later Oct 15, 2018 16:46

Commentary by Dr. Valentin Fuster

commentary composition plaque coronary evolocumab valentin fuster

Circulation August 21, 2018 Issue

Play Episode Listen Later Aug 20, 2018 18:34

Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and it's editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Can we get better at predicting clinical benefit of PCSK9 inhibition based on the severity and extent of coronary artery disease? Well coming right up after these summaries we have an important discussion of an analysis from the FOURIER trial, so stay tuned. The first original paper this week suggests that targeting visceral adiposity may be the crucial step to limit age-related cardiac remodeling and to promote healthy cardiac aging. Co-first authors Drs Sawaki and Czibik, corresponding author Dr Derumeaux, from INSERM France, and their colleagues, hypothesize that since aging induces cardiac structural and functional changes, linked to increase deposition of extracellular matrix proteins including osteopontin, well osteopontin may play a role in myocardial aging. To test this hypothesis, they studied osteopontin-deficient mice and their wild-type litter mates at two and 14 months of age in terms of cardiac structure, function, histology and key molecular markers. They found that during aging, visceral adipose tissue represented the main source of ostepontin and altered heart structure and function via its profibrotic secretome. Furthermore, interventions targeting osteopontin, such as visceral adipose tissue removal and osteopontin deficiency, rescued the heart and induced a selective modulation of fibroblast senescence. This work uncovers ostepontin's role in the context of myocardial aging and suggests that osteopontin may be a potential new therapeutic target for a healthy cardiac aging. The next study shows that higher triglyceride rich lipoprotein cholesterol may be a risk factor for cardiovascular disease and potential therapeutic target. First author Dr Vallejo-Vaz, corresponding author Dr Ray from Imperial College London, and their colleagues assess the relationship between triglyceride-rich lipoprotein cholesterol and cardiovascular risk and whether this risk was modifiable among patients receiving statins in the TNT trial. They found that higher levels of triglyceride rich lipoprotein cholesterol were associated with a significantly higher rate of cardiovascular events among coronary patients treated with statins. Statin therapy reduced triglyceride-rich lipoprotein cholesterol and to a greater extent among those treated with a higher statin dose. Based on their post hoc analysis of the TNT trial, they found that more intensive statin therapy with atorvastatin 80 milligrams, compared to atorvastatin 10 milligrams, resulted in a significantly greater cardiovascular risk reduction among patients with higher triglyceride-rich lipoprotein cholesterol. These results were consistent for higher triglycerides and directionally concordant for non-HDL cholesterol. A higher percentage reduction in triglyceride-rich lipoprotein cholesterol was associated with lower cardiovascular risk independent of LDL cholesterol reduction. Thus, these findings suggest that triglyceride-rich lipoprotein cholesterol is not only a cardiovascular risk marker, but also potentially a therapeutic target. Late gadolinium enhancement on cardiac magnetic resonance imaging represents fibrosis and is seen in 60% of adult patients with hypertrophic cardiomyopathy. However, what about in children and adolescents with hypertrophic cardiomyopathy? First author Dr Raja from University of Copenhagen in Denmark, corresponding author Dr Ho from Brigham and Women's Hospital in Boston, and their colleagues looked at cardiac magnetic imaging data from 195 children and adolescents with hypertrophic cardiomyopathy. Late gadolinium enhancement was present in 46% of patients with overt hypertrophy as opposed to 60% typically represented in an adult population of hypertrophic cardiomyopathy. On the other hand, late gadolinium enhancement was not seen in mutation carriers without left ventricular hypertrophy. In patients who underwent serial imaging, increases in late gadolinium enhancement, left ventricular mass, and left atrial size were detected over two and a half years. Thus these findings in children provide additional insights into the biology and natural history of hypertrophic cardiomyopathy and confirmed that fibrosis is a significant part of the disease process in both children and adults. Whether the adult mammalian heart harbors cardiac stem cells for the regeneration of cardiomyocytes is an important yet contentious topic in the field of cardiovascular regeneration. This week's paper adds to the growing knowledge in this area. First author Dr Li, corresponding author Dr Zhou from Chinese Academy of Sciences and their colleagues developed a new genetic lineage tracing system to label all nonmyocyte populations that contain putative cardiac stem cells. Using dual lineage tracing system, they assessed if non-myocytes generated any new myocytes during embryonic development, adult homeostasis and after myocardial infarction. Skeletal muscles were also examined after injury and acted as internal controls. By using this stem cell marker free and dual recombinases mediated cell tracking approach, the author showed that new myocytes arose from nonmyocytes in the embryonic heart, but not in the adult heart during homeostasis or after myocardial infarction. As positive controls, the same lineage tracing system detected new myocytes derived from nonmyocytes in the skeletal muscle after injury. Thus, this study provides in vivo genetic evidence for non-myocyte to myocyte conversion in the embryonic but not the adult heart. This study also provides a new genetic strategy to identify endogenous stem cells, if any, in other organ systems for tissue repair and regeneration. Well, that wraps it up for our summaries this week, now for our feature discussion. Are there subsets of patients that derive greater clinical risk reduction with the PCSK9 inhibitors? Well we're gonna find out about that right now with a discussion of our feature paper entitled the “Clinical Benefit of Evolocumab by Severity and Extent of Coronary Artery Disease.” So pleased to have with us Dr Marc Sabatine from the TIMI Study Group, who is the first and corresponding author of today's feature paper, as well as our editorialist, Dr Roger Blumenthal from Johns Hopkins University. And of course, we have a familiar voice, a very important editor of our digital strategies and that's Dr Amit Khera from UT Southwestern. Welcome everyone, I think I'd really like to start with maybe asking Roger to paint the background of the importance of this paper. Simply because I just love the title of your editorial, which is “Realizing the Value of PCSK9 Inhibitors: Are We Closer to Finding the Sweet Spot?” I think that really encapsulates it. So Roger, your thoughts? Dr Roger Blumenthal: As Amit Khera knows, I'm a golfer, so when you think about the sweet spot on the club, and we know that PCSK9 inhibitors are a great story of translation from bench to bedside, and we also know that the high cost of the therapy presents a challenge. So what Dr Sabatine and colleagues did was to try to identify the sweet spot for its most effective use and that was a pleasure to comment on Dr Sabatine's excellent study. Dr Marc Sabatine: I think taking a step back I would say from pure biologic perspective, we know that lowering LDL cholesterol will reduce events and that's true and primary and secondary prevention and so if you have therapies that were safe and inexpensive, then I think you wouldn't need to really look for that sweet spot cause it would be all sweet if you will to extend the analogy. But Roger's absolutely right that when you have therapies that are then expensive, then you have to decide, okay in which patients will I get the biggest bang for my buck? And that's a very legitimate question to ask. And so in FOURIER, overall the trial was positive but as we look for subgroups we say, "Can we find individuals who enjoy a greater absolute risk reduction?" Because therefore the benefit cost ratio is gonna be particularly favorable. And so we approach that in a couple different ways. First you can look for just predictors of baseline risk, so if someone has twice the baseline risk and the same relative risk reduction, you should get about twice the absolute risk reduction and therefore the number needed to treat would be cut in half. And so based on our experience from other TIMI trials and other datasets, we looked at three features that have identified patients with higher baseline risks. Amongst those with a history of MI which is in and of itself a heterogeneous group. And so those features were patients with a more recent MI, those with multiple prior MIs and those with known residual multivessel coronary disease. And all three features in the FOURIER dataset, not surprisingly, were predictors of risk with patients having an average about a 50% higher baseline risk. But what was particularly nice was that the subgroups also identified patients who had greater relative risk reduction. And so when you couple the two, the higher baseline risk with the greater relative risk reduction, that translated into greater absolute risk reduction then in each of these high-risk groups, the absolute risk reductions over three years or for CV death, MI, and stroke was around 3% versus around 1% for the low-risk groups. And so that changes the number needed to treat by a factor of three. Dr Carolyn Lam: Wow, that's so cool. Amit, do you think you could just give us a sneak peek into the editors’ discussions when you saw this paper? Dr Amit Khera: This was an easy one, it's clearly a very important paper and if you step back 10,000-foot view, these drugs were initially approved based on LDL lowering and people were using them without knowledge of whether or not they actually lowered events. Marc's group and others have now shown us that certainly they do lower events, but really the next most important thing is application. Who should we use them in and when should they be used and where might they be most effective and I think it was said out in the introduction of this paper, this idea of personalized medicine. And I think this really is an important step forward, not just for PCSK9 field but in general, how we should be thinking about drugs, about balancing cost and benefits and who would benefit most. So maybe one analogy, I think PCSK9 was not prescribed as much as they had been predicted given costs and other considerations and maybe with analysis like this they've hit it out of the rough back on the fairway, I threw that in for you, Roger. And I do have one question for Marc, which is this is clearly important to better define who would benefit the most and I guess in terms of action abilities, the goal here to provide guidance for clinicians where, you know, if I'm seeing a patient this morning I would take this into account or is this something larger where we recently saw with alirocumab, they changed pricing based on sub-group analysis of a higher risk group. How do you think we should move forward with this type of information? Dr Marc Sabatine: I’ll get back to the point I raised earlier, I do want to underscore that I think that the true biologic notion is that all these patients, sub-types of secondary prevention or primary prevention all benefit from LDL lowering. So I wouldn't want people to walk out with the notion that it's the only subset that would benefit and really from a population level, obviously Roger's in a better position to speak about this, but sort of shifting the population LDL lower in general would have a huge impact on the risk for cardiovascular disease. But to your question Amit, looking in for a patient in front of you, I think it's quite fair to say right now there's this kind of tug of war back and forth between payers and clinicians. Clinicians saying, "I have a patient in front of me, they have known atherosclerotic cardiovascular disease, I wanna lower their risk, I wanna manage their risk factors and I wanna get their LDL cholesterol lower and I have a bunch of great tools in front of me." Statin for sure is the foundation, maybe acetamide and PCSK9 inhibitors. And then payers saying, "Well wait a minute, these are expensive drugs and so we're gonna try to restrict that and create a lot of hoops for clinicians to jump through." And so I would rather than wasting all that time back and forth, I think it is logical to say, "What are the high-risk groups?" Where we can agree there's the large enough absolute risk reduction that for a given cost, that makes sense. Allow there to be alignment for that and have clinicians just be able to write a script and have it filled rather than wasting a lot of time with preauthorization and letters back and forth. Dr Amit Khera: That's a great point, maybe I'll just take one follow-up, which is now trying to sift through all the high-risk groups and they end up maybe becoming a bit of a Venn diagram. I know in Roger's editorial he talked about the other FOURIER analysis with PAD and there's more groups to come or do we have enough of a starting place where we think we have enough for decision making? Dr Marc Sabatine: I would say there are a variety of groups, there is some overlapping even in the paper then we looked at the union of those three high-risk features, which identified about two thirds of the patients who were enrolled in the trial with a history of MI. But you're right, the other slices of the data that will also identify high risk groups, PAD is a particularly good one because most of the therapy for those patients has focused on antithrombotic therapy, which always will have some downside for increased bleeding, whereas risk factor modification in this case has no downside. So that's a very high-risk group, it certainly is important to focus on. But I think within the MI subset, this is a great place to start the other analyses we're doing. And probably after we've sort of finished the series of, if you will, these kind of univariant slices, then we'll try to put that together into a more comprehensive picture. Dr Roger Blumenthal: We tried to say that we still need the formal cost-effective analyses in these specific high-risk groups, but it seems most reasonable to focus on engaging in shared decision making now with our patients about PCSK9 inhibitor use and those with a recent ACS and the basis of Odyssey Outcomes and we're awaiting the final publication of that. Symptomatic peripheral arterial disease, which Marc previously published in Circulation, and then looking at these high-risk features that was the subject of this article, those with a more recent MI within the past two years, multiple prior MIs and residual multivessel coronary disease. And one of the things that we especially found interesting was among the more than 8,000 individuals without a high-risk feature, the event rates were nearly unchanged in the evolocumab versus placebo groups. So I think that's very important, but one other point that we have to keep in mind is that the focus of the last set of guidelines and probably the next cholesterol guidelines that likely will be out in November, will have a large component of the shared decision making and we need to see where the cost comes down, whether these companies that make these medications will be able to significantly lower the cost in a reproduceable manner and patients and clinicians will have to jointly decide what to do, do we add acetamide? Do we add a PCSK9 inhibitor? But we finished our editorial saying that all clinicians and patients should currently pursue a comprehensive lifestyle and medical regimen for secondary prevention. We all have to remember that and if a person's LDL, a high-risk individual is at least 70 with high-risk features and certainly above 100 on maximum tolerated statin therapy, it's important to strongly consider a PCSK9 inhibition and it'll be very interesting to see what the final wording is when the ACC/AHA cholesterol guidelines come out in November. Dr Carolyn Lam: Amit, would you like to add any further take-home for the clinicians listening in? Dr Amit Khera: I just first want to congratulate both of these discussions today, I think the paper was so incredibly important and I think Roger's group really helped frame it well in the field. The one thing I'd say is this is a moving target, we have some early guidance now that I do think is actionable, so I actually have clinic in about an hour and I'm sure I'll be thinking about this as I think about how to apply PCSK9. Which groups might benefit most, so I do think this is actionable now, I think the points that were made about cost effective analysis, how do we bundle all these concepts or high risk patients into maybe an algorithm and how do the guidelines interpret this as a moving target. We'll wait to see, but I do think there's some important actionable information even now for our clinical patients. Dr Carolyn Lam: I just love that, and you know that is just so much in line with the ethos of what Circulation is about now. We really, really love the papers that you have to pick up because they're of immediate applicability to your clinical practice. Well audience, you heard it right here. Thank you so much for joining us this week and of course don't forget to tune in again next week.

P077 - Evolocumab e bococizumab em pacientes com DCV - FOURIER e SPIRE - Rodrigo de Oliveira Moreira

SBD

Play Episode Listen Later May 14, 2018 8:27

Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017 Mar 17; Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients. N Engl J Med. 2017 Mar 17

safety patients oliveira moreira spire pacientes cardiovascular diseases new england journal of medicine fourier clinical outcomes evolocumab

Why Cholesterol Levels Have No Effect on Cardiovascular Disease (And Things to Think about Instead)

Nourish Balance Thrive

Play Episode Listen Later Apr 16, 2018 119:00

Dr. Malcolm Kendrick is a medical doctor, author, speaker, and sceptic living in Cheshire, England. His evidence-based arguments refute the lipid hypothesis and other ideas related to chronic illness that has resulted in a pervasive culture of fear and misinformation. His popular blog features an ongoing series of posts on the real causes of heart disease, pointing to endothelial damage as a causal factor and nitric oxide as vital for preserving health. Dr. Kendrick is with us to share not only what really causes cardiovascular disease, but the specific environmental and psychosocial factors that cause the most harm, and what we need to do to maintain good health. We also discuss unexpected side effects of common medications and supplements and the healing power of specific micronutrients. If you enjoy this podcast, you can support Dr. Kendrick’s work by pre-ordering his latest book, A Statin Nation: Damaging Millions in a Brave New Post-Health World, available 7/12/18. Here’s the outline of this interview with Malcolm Kendrick: [00:01:05] Book: The Great Cholesterol Con: The Truth About What Really Causes Heart Disease and How to Avoid it, by Malcolm Kendrick. [00:01:07] Book: Doctoring Data: How to Sort Out Medical Advice from Medical Nonsense, by Malcolm Kendrick. [00:01:14] The International Network of Cholesterol Skeptics (THINCS). [00:01:46] Trail Runner Nation Podcast: Metabolic Flexibility with Christopher Kelly. [00:02:59] Highlights email series. [00:03:01] Podcast: The True Root Causes of Cardiovascular Disease, with Jeffry Gerber. [00:03:07] Blog series: What causes heart disease? [00:05:28] Study: Hayashi, Keiko, et al. "Laughter lowered the increase in postprandial blood glucose." Diabetes care 26.5 (2003): 1651-1652. [00:06:20] Stress hormones, sympathetic nervous system. [00:07:32] Graph: Lithuanian death rate; Study: Kristenson, Margareta, et al. "Increased psychosocial strain in Lithuanian versus Swedish men: the LiVicordia study." Psychosomatic Medicine 60.3 (1998): 277-282. [00:08:25] Paul Rosch, M.D, founder of the American Institute of Stress. [00:10:20] Endothelium, glycocalyx. [00:11:12] Nitric Oxide (NO). [00:11:37] Alfred Nobel, nitroglycerin (glyceryl trinitrate, or GTN), Viagra. [00:13:13] Study: Andersson, Daniel P., et al. "Association between treatment for erectile dysfunction and death or cardiovascular outcomes after myocardial infarction." Heart (2017): heartjnl-2016. [00:13:39] Sunlight as nitric oxide stimulant. [00:14:45] Vasculitis, Systemic lupus erythematosus (SLE), Rheumatoid arthritis, Sickle-cell disease. [00:17:05] Endothelial progenitor cells. [00:17:55] Carl von Rokitansky, Rudolf Virchow. [00:21:19] Endothelial damage required for arterial plaque. [00:21:52] Study: Law, M. R., and S. G. Thompson. "Low serum cholesterol and the risk of cancer: an analysis of the published prospective studies." Cancer causes & control 2.4 (1991): 253-261. [00:23:49] Study: Ravnskov, Uffe, et al. "Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review." BMJ open 6.6 (2016): e010401. [00:25:03] Statins increasing NO, studies: 1, 2, 3. [00:26:52] Study: Lanphear, Bruce P., et al. "Low-level lead exposure and mortality in US adults: a population-based cohort study." The Lancet Public Health (2018). [00:28:17] Corticosteroids. [00:30:25] Familial Hypercholesterolemia. [00:34:56] Study: Winnik, Stephan, et al. "Systemic VEGF inhibition accelerates experimental atherosclerosis and disrupts endothelial homeostasis–implications for cardiovascular safety." International journal of cardiology 168.3 (2013): 2453-2461. [00:36:29] QRISK survey for heart disease. [00:41:21] Inflammation as healing. [00:42:40] Study: Willis, G. C. "The reversibility of atherosclerosis." Canadian Medical Association Journal 77.2 (1957): 106. [00:44:36] Corticosteroids reduce inflammation, increase CVD risk, NSAIDs. [00:45:05] Study: Guilhem, Gaël, et al. "Effects of air-pulsed cryotherapy on neuromuscular recovery subsequent to exercise-induced muscle damage." The American journal of sports medicine 41.8 (2013): 1942-1951. [00:49:06] Lipoprotein A. [00:51:27] Vitamin C deficiency as possible cause of CVD. [00:53:01] Study: Lee, A. J., et al. "Plasma fibrinogen and coronary risk factors: the Scottish Heart Health Study." Journal of clinical epidemiology 43.9 (1990): 913-919. [00:55:27] Diabetes, triglycerides, sepsis, gingivitis as procoagulants. [00:58:39] Major endothelial offenders. [01:00:03] Study: Escolar, Esteban, et al. "The effect of an EDTA-based chelation regimen on patients with diabetes mellitus and prior myocardial infarction in the Trial to Assess Chelation Therapy (TACT)." Circulation: Cardiovascular Quality and Outcomes (2013): CIRCOUTCOMES-113. [01:01:03] Study: Douaud, Gwenaëlle, et al. "Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment." Proceedings of the National Academy of Sciences 110.23 (2013): 9523-9528. [01:01:44] Study: Marik, Paul E., et al. "Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study." Chest 151.6 (2017): 1229-1238. [01:02:27] Allen Smith, dying of flu, recovered with Vitamin C. [01:03:13] sunlight, viagra, stress management, alcohol. [01:04:23] Blue zones, strong social relationships. [01:05:07] Lifestyle and environmental factors associated with lower life expectancy. [01:13:05] Statins. [01:15:49] Absolute risk vs. relative risk; side effect vs. adverse effect, adverse events. [01:21:07] Problems caused by statins. [01:21:29] CoQ10, ATP. [01:23:47] Placebo effect, nocebo effect. [01:24:40] Study: Gupta, Ajay, et al. "Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase." The Lancet 389.10088 (2017): 2473-2481. [01:25:45] Study: Cohen, Jerome D., et al. "Understanding Statin Use in America and Gaps in Patient Education (USAGE): an internet-based survey of 10,138 current and former statin users." Journal of clinical lipidology 6.3 (2012): 208-215. [01:26:32] PCSK9 inhibitors. [01:27:54] Study: Sabatine, Marc S., et al. "Evolocumab and clinical outcomes in patients with cardiovascular disease." New England Journal of Medicine 376.18 (2017): 1713-1722. [01:35:16] L-arginine, citrulline. [01:39:34] Study: Tunstall-Pedoe, Hugh. "Does dietary potassium lower blood pressure and protect against coronary heart disease and death? Findings from the Scottish Heart Health Study?." Seminars in nephrology. Vol. 19. No. 5. 1999. [01:40:40] Study: Graudal, Niels. "A radical sodium reduction policy is not supported by randomized controlled trials or observational studies: grading the evidence." American journal of hypertension 29.5 (2016): 543-548. [01:43:55] Groupthink, cognitive bias. [01:44:21] Michael Alderman, M.D. [01:44:48] Evolutionary Psychology. [01:45:58] Peer Review. [01:51:36] Study: Bronstein, Alvin C., et al. "2010 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 28th Annual Report." Clinical Toxicology 49.10 (2011): 910-941. [01:52:57] Book: A Statin Nation: Damaging Millions in a Brave New Post-Health World, by Malcolm Kendrick. [01:57:37] drmalcolmkendrick.org.

america american england stress international heart medicine lifestyle cancer blog trial journal lack ga effects thompson swedish levels diabetes laughter vol sciences absolute increased outcomes gaps american association inflammation chest national academy systemic findings viagra placebos atp vitamin c sunlight plasma cholesterol american institute lancet niels proceedings seminars cheshire new england journal adverse lithuanian cardiovascular diseases annual reports groupthink bmj keiko nsaids statins sickle cvd alfred nobel coq10 evolutionary psychology sle daniel p rheumatoid marcs peer review international network corticosteroids paul e uffe gwena vasculitis pcsk9 endothelial edta allen smith preventing alzheimer canadian medical association journal psychosomatic medicine familial hypercholesterolemia hydrocortisone christopher kelly gtn endothelium rudolf virchow clinical toxicology evolocumab

Circulation January 23, 2018 Issue

Play Episode Listen Later Jan 22, 2018 18:11

Dr. Carolyn Lam: Hello from the American Heart Association meeting in Anaheim. I'm Dr. Carolyn Lam, associate editor from Circulation at National Heart Centre in Duke National University of Singapore and I'm so pleased to be here with the Circulation team led by editor in chief Dr. Joe Hill, as well as with Dr. Laura Mauri, senior editor from Brigham and Women's Hospital, and Dr. Dharam Kumbhani, associate editor from UT Southwestern. Boy, we've got lots to discuss. I mean, I want to just first start with congratulating you, Joe. We have got quite a number of simultaneous publications here at the AHA. Dr. Joseph Hill: I appreciate that, Carolyn. Don't congratulate me. We have a team that is a privilege to work with. One of the initiatives that we launched right from the start was a desire to foster and shine a bright light on emerging science at the major meetings around the world. Often, that involves simultaneous publication. I'm proud to say that we have 11 simultaneous publications, a record for us here at AHA. Most of them are clinical trials. A few are clinical science, and two of them are young investigators who are competing in the various different competitions. We reached out to them a few weeks ago and offered them the opportunity to submit to us, of course with no guarantees, and our standard remains the same, but we promised that we would provide them with an external peer review. Two of them made it through the process and they will be simultaneously published with their presentations here in Anaheim. Dr. Carolyn Lam: Wow, well you heard it. A record 11 simultaneous publications. We've got a lot to talk about. Let me just maybe group the topics a little bit. Let's start with talking about peripheral artery disease. I think there are at least three papers around that area, and then we'll talk about coronary artery disease, and almost focusing more on implementation science, papers, there are two there, and then of course we have to talk about heart failure. Dharam, could you start? Tell us about the FOURIER PAD trial. Dr. Dharam Kumbhani: Yeah. It's very exciting to have clinical trials in the PAD realm. FOURIER PAD is certainly really well done sub-study of the FOURIER trial. As you remember, this was a landmark trial, which compared a PCSK9 inhibitor Evolocumab in two doses, two placebo. The overall trial was done in about 27,000 patients who were followed for a median of 2.2 years. In this trial, Marc Bonaca and investigators, they looked at the PAD subset, which were about 13% of the total cohort. Now, they specifically set out to look at how patients with PAD, during this trial and very gratifyingly, they also specifically assessed how patients with PAD did as far as limb events, not just cardiovascular events. At the outset, not surprisingly, patients with PAD had a higher risk of cardiovascular events by, I think it was about 60% higher for the primary end point compared with patients who did not have PAD. There was really no, in fact, modification by PAD in that the benefit of Evolocumab that we saw in the overall trial was preserved among the patients with PAD as well as those without PAD. However, because patients with PAD had higher event rates, the absolute risk reductions were higher in patients with PAD. Then, these investigators looked specifically at the incidents of major adverse limb events, which is a composite of acute limb ischemia, urgent revasc, and major amputations. What they show is that in the overall cohort, there is a 42% reduction in the risk of these major adverse limb events with Evolocumab compared with placebo. Obviously, the effect is significantly higher in patients with PAD. Although the benefit wasn't noted in the PAD subset specifically, the overall p-value for interaction was negative. One of the really exciting things about this paper is that just like investigators have shown a monotonic reduction in cardiovascular event rates with LDL reduction, similarly, the investigators show a reduction in limb events, which is dose related and the same way in a monotonic fashion with Evolocumab. I think this is really exciting and I think this will be a very important paper for the field. Dr. Carolyn Lam: Yeah. Dharam, that was beautifully summarized but once you start talking about the peripheral artery disease and this lack of interaction on effects and so on, I think of the CANVAS trial results that were reported at this meeting too. If I could maybe briefly summarize what the authors did in this circumstance, they looked at the more than 10,000 patients in the CANVAS trial who were randomized into Canagliflozin versus placebo in diabetic patients but this time they looked at whether or not there was a difference in effect with the primary prevention cohort versus the secondary prevention. Primary prevention meaning those adults who had diabetes and risk factors but no established cardiovascular disease and the secondary prevention were those with peripheral artery disease, for example, and other established cardiovascular disease. The same thing, a lack of interaction, which I think is really important because it was the same sort of idea that the overall risk of cardiovascular events was lower in the primary prevention group. Looking at them as a subgroup alone, you didn't get the p-value that crossed the limit because the power was less in a lower risk group, but the lack of statistical interaction really gives us additional information, I think, that Canagliflozin and maybe the SGLT2s in general may be effective for primary prevention in diabetic patients. What do you think? Dr. Dharam Kumbhani: Yeah. I mean, I think certainly, very interesting findings along those lines. As you pointed out, the event rates are much lower in the primary prevention cohort. All the confidence intervals overlap one, but because all the p-values for interaction for the three-point maze, the four-point maze, et cetera, one would say that there really isn't a difference between the primary and the secondary prevention subgroups. You would potentially have the same benefit in that subgroup as well. Dr. Carolyn Lam: Fortunately or unfortunately, in that same study, they looked at the risk of amputations and there was a lack of interaction too for that meaning there was a higher risk of amputations with Canagliflozin versus placebo. That of course is a really hot topic now, isn't it? I just wanted to point out though, when you look at it in the primary prevention group, there are only 33 events. What do you think? It spells caution but further look needs to be done? Yeah. Contrast that with the EMPA-REG outcome PAD analysis. You want to tell us about it? Dr. Dharam Kumbhani: Yeah. Once the Canagliflozin CANVAS findings came out showing a high rate of amputations with Canagliflozin, the Empagliflozin, the EMPA-REG outcome's investigators went back and looked at the PAD subset in EMPA-REG outcomes. This was about 20% of the total cohort. I will say that unlike FOURIER, which we just discussed, the ascertainment of amputations was not prospectively defined for this trial and it was really obtained from the CRF forms. However, having said that, it did not appear that amputation rates were higher with Empagliflozin. They did not break it down by the different doses but one assumes that the benefit is consistent between the two doses that they study. One would imagine the PAD patients would have a higher rate overall, which it was, but even in that group, it was about 6% over three years and there was really no difference between the patients who received Empagliflozin versus those who got placebo. Dr. Carolyn Lam: That EMPA-REG outcome paper, I mean, interestingly, it was a research letter. Joe, you've been watching this whole field unfold right now and our journal has published so many good papers, including CVD REAL, all in this space. Could you comment on that a little bit and the research letter concept and the fact that we're publishing so many of these interesting papers in this topic? Dr. Joseph Hill: Well, Carolyn, as you inferred, this field is evolving very rapidly. Now, the interface between metabolic disease and diabetes and heart disease is blurring. Some of these diabetic drugs are really emerging as heart failure drugs, it looks like and so there's a great deal of interest in exploring that and trying to find underlying mechanisms. It's an incredibly exciting time. In parallel with that, we are publishing research letters now for papers where, again, our bar starts with validity. Our bar doesn't change but if it's a story that can be communicated with really one multi-paneled figure and an 800word text, then that is a nice bite-size piece of information that we can get out to our readership. We're publishing one or two a week now. Overall, it appears to be well received and I think it's an effective vehicle for conveying certain types of our content. Dr. Carolyn Lam: Frankly, it's such a delight to read, isn't it? It's hard to write. I think the shorter, the harder to write but this just goes to show how equally important they are. Dr. Joseph Hill: Absolutely. Dr. Carolyn Lam: That we're discussing it here. Well, let's go on to the next topic then, coronary artery disease. Regionalization of the care. I'll say that again, regionalization of the care. Would you like to comment on the two papers that are simultaneously being published? One would be the ACCELERATOR-2 trial. That's in the U.S. Then, a second from New Zealand, the ICare-ACS trial. Slightly different but- Dr. Joseph Hill: Well, that's exactly right. Often, we know what to do but we don't do what we know we need to do in medicine. The implementation of what we already know is an area of hot research and is an area that's evolving rapidly. These two studies, ACCELERATOR-2 here in the United States, focused on regionalization of the interface between EMS systems and EDs, how to get patients identified in the hospital to their device, whether it's a stent or a balloon pump or whatever it is. The first medical contact to device was the metric and by implementing what we already know, the AHA mission lifeline principles, these investigators were able to optimize this regionalization, so there wasn't so much variability across these 12 metropolitan regions. As a consequence, the time to first medical contact to device was shortened, and there was in fact a striking, maybe even surprising, mortality benefit. Dr. Carolyn Lam: Exactly. That was striking to me too. Dr. Joseph Hill: From the street to the lab, another paper from New Zealand that you referred to called ICare-ACS focused on doing a better job in the emergency department with serial ECGs and serial high sensitivity troponins, risk stratification algorithms and they found that, again, by developing these clinical pathways within the ED, they were able to shorten the length of stay in the ED and the length of stay in the hospital. Dr. Carolyn Lam: Yeah. I thought those were amazing and then also from different parts of the world, really strong public health messages as well. Laura, you take care of these ACS patients right on there. What did you think of these papers? Dr. Laura Mauri: No, I agree. I think that we've, in the past, focused on science and focused on clinical trials but ultimately, none of that matters if we don't deliver the healthcare to the patient. I think this is just a growing field and I'm glad that we're emphasizing it in circulation. Dr. Carolyn Lam: Absolutely. If we would now go to another area that is really increasing in prevalence throughout the world. Heart failure, and of course, heart failure with preserved ejection fraction. Dr. Joseph Hill: Your favorite topic. Dr. Carolyn Lam: Congratulations, Laura on the paper that you're presenting, that is being presented at this meeting, the REDUCE LAP trial. Could you tell us a little bit more about that? Dr. Laura Mauri: Sure. Yes, as you know, it's a really challenging field, heart failure with preserved ejection fraction. There aren't a lot of therapies that we have. We really don't have great medical therapy. This study actually looks at a medical device to treat patients. It really is a feasibility study, so it's a relatively small trial, just over 90 patients but it's randomized. We know in the device arena, as in all trials, how important randomization is but also blinding. This was actually a sham-controlled blinded trial really designed to look at this interatrial shunt device in patients who have an elevated wedge pressure. The REDUCE LAP stands for reduce left atrial pressure. That was the primary endpoint, was pulmonary capillary wedge pressure. This was not only looked at the safety, which showed that the device placement was very safe, but at the same time also looked at the proof of concept that by placing the shunt device, there was actually a reduction in wedge pressure over a period of exercise. It needs to be followed on. It's certainly just the first phase of trials but a pretty good standard with the sham control. Dr. Carolyn Lam: Yeah, well, congratulations again. I mean, this follows … There was a previous publication of the single arm trial and now, this is the first randomized sham-controlled, and the results are consistent. It's a very difficult trial to carry out. HFpEF patients are notoriously difficult to recruit. Could you tell us a little bit about what it was like successfully completing this trial? Dr. Laura Mauri: Yeah. Well, we had very enthusiastic centers and principal investigators, Ted Feldman and Sanjiv Shah. I think what it really required in this early phase was sites that were committed to characterizing the exercise physiology. The next stage of rolling this out to a broader number of sites and a larger number of patients to see if there's a clinical effect will really be more focused on the clinical endpoints and quality of life because ultimately that's the goal, is to improve symptoms in these patients. Dr. Carolyn Lam: What I love about the design and the whole concept, it's so simple and elegant. We almost sometimes forget that HFpEF is heart failure, which means that by definition, there's raised filling pressures. It's hemodynamic at the end and this is just a simple concept of offloading the left atrium. That's so beautiful but it does come with some questions. Every time you mention this to someone, they go, “What about, I don't know, Eisenmenger's syndrome developing later?” The right side, volume overload, pulmonary hypertension, what about atrial fibrillation down the line? How about the safety parts of it? Dr. Laura Mauri: Right, so the procedural safety was excellent but then I think you raise really important questions and these patients are still in follow-up but looking at the report here at this meeting, there was no pulmonary hypertension in excess in the shunt treated arm. The patient selection was towards patients who had higher wedge compared with right atrial pressure and among those patients, there was no evidence of RV overload. At least at this stage things look good to go on to the next step. Dr. Carolyn Lam: That's wonderful and exciting. We definitely need a therapy for HFpEF. Joe, would you like to highlight any other trial? We have 11. We've discussed six. Dr. Joseph Hill: Tonight at the editorial board meeting, we will be saluting these two young investigators who are presenting their work in this competition and simultaneously publishing their work. We've invited these young investigators and their mentor and they will present a short talk to the editorial board dinner. It's an effort to salute and recognize these early career investigators, to congratulate them on outstanding work. We're pleased and privileged to publish it, so I'm particularly excited about that. Dr. Carolyn Lam: Wow, Joe. That is great. Thank you. I didn't know that was happening either. That's fabulous. Dharam or Laura, any other highlights that you may want to mention in this meeting? Dr. Laura Mauri: I think that it's just been a wonderful kickoff to the meeting. We've covered, I think, many of the really important trials so it's really exciting to be able to see the work in print. Dr. Carolyn Lam: That's great, and to discuss it as well. Dr. Dharam Kumbhani: Yeah, I agree. This is really exciting and hopefully, we can keep growing from strength to strength every year. Dr. Carolyn Lam: Yep. You heard it right here everyone. We are going to grow from strength to strength under your leadership and with this great team, so thank you very much for joining us today.

FOURIER – Evolocumab and Outcomes in PAD

Cardiology Now

Play Episode Listen Later Nov 12, 2017 5:58

Dr. Marc Bonaca and Dr. C. Michael Gibson Discuss

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The Hurry for FOURIER & What's New From HERDOO2 – Decision Making in VTE and Evolocumab for CVD Risk Reduction

The Rounds Table

Play Episode Listen Later May 5, 2017 29:51

It is widely accepted that statin drugs reduce cardiovascular risk. However, how much of this risk reduction is attributable to LDL cholesterol reduction as opposed to something intrinsic in the statin drug has been a matter of debate. Paxton takes listeners through a randomized controlled trial that evaluated the efficacy of evolocumab (a biologic PCSK9 ...The post The Hurry for FOURIER & What's New From HERDOO2 – Decision Making in VTE and Evolocumab for CVD Risk Reduction appeared first on Healthy Debate.

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The Hurry for FOURIER & What's New From HERDOO2 – Decision Making in VTE and Evolocumab for CVD Risk Reduction

The Rounds Table

Play Episode Listen Later May 5, 2017 29:52

It is widely accepted that statin drugs reduce cardiovascular risk. However, how much of this risk reduction is attributable to LDL cholesterol reduction as opposed to something intrinsic in the statin drug has been a matter of debate. Paxton takes listeners through a randomized controlled trial that evaluated the efficacy of evolocumab (a biologic PCSK9 ... The post The Hurry for FOURIER & What's New From HERDOO2 – Decision Making in VTE and Evolocumab for CVD Risk Reduction appeared first on Healthy Debate.

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Pharmapills podcast puntata n. 1. Novità, curiosità e lavoro dal mondo del Farmaceutico.

Play Episode Listen Later Mar 22, 2017 12:33

Pharmapills - Pillole dal farmaceuticoNovità, Curiosità e Lavoro dal mondo del Farmaceutico. A cura di Stefano Lagravinese.In questa puntata parliamo di:Aziende: Astrazeneca, AbbVie, Angelini, Bayer, GSK, Laboratori Abbott, Amgen, Pfizer, Novartis, Roche, Eli Lilly, Johnson & Johnson, Recordati, Fidia Farmaceutici, Therabel, Mediolanum Farmaceutici e Ifom.Persone: Fabrizio Greco (AbbVie Italia), Egiziano Iencinella (Angelini), Amelia Parente (Roche), Jean-Michel Robert (Therabel), Valter Longo (Ifom) e Massimo Scaccabarozzi (Farmindustria).Nuove terapie: Evolocumab, Ulipristal acetato e Rivaroxaban.Patologie: cirrosi epatica, fibrosi polmonare, diabete, osteoporosi, artrite, progeria, fibromi uterini, coronaropatia o arteriopatia periferica, amiloidosi, porfiria ed emofilia.Ogni mercoledì alle h 12.00 su Spreaker.com e iTunes.Per approfondire gli argomenti visita il sito web www.PharmaPills.it e clicca mi piace sulla pagina facebook “PharmaPills”. Ricevi ulteriori informazioni e nuovi contenuti in tempo reale tramite il canale telegram www.telegram.me/pharmapills.Gli autori:- Linda Scannavini (speaker)- Giorgia Latteri (montaggio)- Stefano Lagravinese (regia e cordinamento)Contatto diretto: pharmapills [chiocciolina] carrieranelfarmaceutico.com

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Pharmapills podcast puntata n. 1. Novità, curiosità e lavoro dal mondo del Farmaceutico.

Play Episode Listen Later Mar 22, 2017 12:33

Cholesterol-lowering drug, Defibrillators, Post-traumatic stress disorder and heart disease, Lack of drugs in pregnancy

Inside Health

Play Episode Listen Later Mar 21, 2017 27:55

Statins have dominated the cholesterol-lowering field for some years but last week the results of an international trial of Evolocumab, one a new breed of medicines for reducing cholesterol, was hailed as a breakthrough. Professor Peter Sever, one of the leaders of the trial, explains how Evolocumab differs from statins and Dr Margaret McCartney takes a look at the trial. You may have noticed them in work places, gyms, and other public spaces but do you know how and when to use a defibrillator? Every time someone has a cardiac arrest and CPR is performed we should also be running for the nearest defibrillator. But currently this only happens in 2-3% of cardiac arrests, putting thousands of lives at risk every year. Mark speaks to teacher Erica Melsom and the pupil, Alex Cowes, whose life she saved by using the school defibrillator. Professor Gavin Perkins explains why and when we should run and get one. And Mark demonstrates just how simple they are to use, even if you've never touched one before. Posttraumatic Stress Disorder, a psychological condition which can begin after a traumatic event and last for many years, is the equivalent for your cardiovascular system of smoking 10 cigarettes a day. Dr Donald Edmondson explains how extreme stress takes a toll on our arteries. More than 80% of pregnant women take at least one prescribed medication and yet very few of these drugs are actually licensed for use in pregnancy. Mark talks to Professor Anna David about why there has been a reluctance to license medications for use in pregnancy, what impact that has for pregnant women, and what needs to change. Producer: Lorna Stewart.

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FirstWord Pharmaceutical News for Tuesday, November 11, 2014

Play Episode Listen Later Nov 11, 2014 7:24

Today in FirstWord:

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FirstWord Pharmaceutical News for Friday, August 29, 2014

JAMA Editors' Summary: On research in medicine, science, & clinical practice. For physicians, researchers, & clinicians.

Play Episode Listen Later Aug 29, 2014 10:12

Today in FirstWord:

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Effect of PET before liver resection on surgical management of CRC metastases, effect of adding evolocumab vs ezetemibe to statins, review of glaucoma management, and more.

Play Episode Listen Later May 13, 2014 5:25

Editor's Audio Summary by Edward H. Livingston, MD, Deputy Editor, the Journal of the American Medical Association, for the May 14, 2014 issue

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FirstWord Pharmaceutical News for Monday, March 31, 2014

Play Episode Listen Later Mar 31, 2014 15:56

Today in FirstWord:

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FirstWord Pharmaceutical News for Tuesday, March 18, 2014

Play Episode Listen Later Mar 18, 2014 10:51

Today in FirstWord:

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FirstWord Pharmaceutical News for Friday, January 24, 2014

Play Episode Listen Later Jan 24, 2014 8:35

Today in FirstWord:

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FirstWord Pharmaceutical News for Thursday, November 21, 2013