136. ACC 2021 Prevention Highlights – ADAPTABLE and STRENGTH Trials

Join CardioNerds for a great discussion about key ACC 2021 Prevention highlights featuring the ADAPTABLE and STRENGTH trials. This episode is produced in collaboration with the American College of Cardiology Prevention of Cardiovascular Disease Council with mentorship from the Council’s Chair Dr. Eugene Yang (University of Washington Medical Center) who provides a message at the end of the episode.  

First, Dr. Amit Goyal and Council Representative Dr. Mahmoud Al Rifai (FIT, Baylor College of Medicine) discuss the implications of the ADAPTABLE Trial with Dr. Gina Lundberg (Emory University School of Medicine).  

Then Dr. Tommy Das (FIT, Cleveland Clinic), Dr. Rick Ferraro (FIT, Johns Hopkins) and Council Representative Dr. Anum Saeed (FIT, University of Pittsburgh Medical Center) discuss the results of the STRENGTH trial’s secondary analysis with Dr. Steven Nissen (Cleveland Clinic).  

Disclosures: Dr Nissen reported grants from AstraZeneca during the conduct of the STRENGTH trial

Show notes


The ADAPTABLE trial is a randomized open label pragmatic trial comparing two doses of aspirin (325 mg vs. 81 mg) for the secondary prevention of cardiovascular disease. The trial employed a range of innovative and low-cost methods to simplify the identification, recruitment, and follow-up of patients. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke. The primary safety outcome was hospitalization for major bleeding. 

A total of 15,076 patients were followed for a median of 26.2 months. The primary effectiveness and safety outcomes were not significantly different between the two groups. Together with Dr. Lundberg we discuss design and methodological issues related to the trial and applicability to clinical practice.  

  • ASA 81 mg is as effective as ASA 325 mg for reducing cardiovascular events 
  • ASA 325 mg does not cause more bleeding episodes than ASA 81 mg 
  • ASA dosing should be based on a clinician-patient risk discussion incorporating patients’ risk profile and their values and preferences  
  • Future trials should ensure adequate representation of women and race/ethnic minorities  

The results of the present trial suggest that either dose of ASA (81 mg or 325 mg) would be adequate to lower patients’ risk of death or atherosclerotic cardiovascular events with similar risk of bleeding. ASA dosing should be based on patient values and preferences and clinician judgement as the effectiveness and safety profile of these two regiments appears to be equivalent on the basis of the present trial.  

STRENGTH Trial, Secondary Analysis 

Whether omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce cardiovascular risk has been long debated. Data have largely remained inconclusive with several previous trials, particularly the VITAL and ASCEND, showing no significant cardiovascular benefit DHA and EPA supplementation. However, the REDUCE-IT and the JELIS trials showed cardiovascular benefit with higher dose of purified EPA compared to placebo.  Meanwhile, the STRENGTH trial did not show any difference in CVD outcomes in treatment groups using a combined EPA/DHA formulation. 

In this episode, we discuss a secondary anaylsis from the STRENGTH trial entitled “Association Between Achieved ω-3 Fatty Acid Levels and Major Adverse Cardiovascular Outcomes in Patients With High Cardiovascular Risk” presented at the ACC 2021 addressing the effects of carboxylic acid formulation of EPA/DHA (omega-3 CA) compared with placebo among patients with dyslipidemia and high cardiovascular risk.  

This analysis showed that there was no added clinical benefit or harm in those who achieved the highest tertiles of EPA and DHA. 

  • “It is very important to use a neutral comparator as a placebo and this is what we aimed to do in the STRENGTH trial by using corn oil as the placebo against EPA/DHA… you can only optimally interpret a clinical trial in the context of a neutral placebo.”  
  • The STRENGTH trial used carboxylic acid derivative which is better absorbed than other ester formulations used in other studies and its absorption is independent of food. 
  • The EPA concentration in the blood reached adequate levels (even up to 268% in the pooled analysis) in this study however, there was only a ~39% increase in DHA even though a formulation of both EPA and DHA was used. Reasons for this remain to be uncovered.  
  • Three most recent trials including REDUCE-IT, STRENGTH and OMEMI trial have all consistently showed an increase in atrial fibrillation with omega-3 FA use. The incidence is small but not trivial. Mechanistically, we do not know the reason for this.   
  • Opportunity to do further studies studying the effects of Omega-3FA on atherosclerotic disease itself and its progression or reduction remains wide open.  

Guest Profiles

Dr. Yang is medical director of the UW Medicine Eastside Specialty Center and a UW professor of medicine. He has particular expertise in the diagnosis and treatment of coronary artery disease, valvular heart disease, peripheral vascular disease, congestive heart failure, cardiac arrhythmias, hypertension and lipid disorders. He is especially interested in the primary and secondary prevention of heart disease through aggressive risk-factor modification and lifestyle change. He also conducts research on new cholesterol-lowering therapies and appropriate treatment options for patients with coronary artery disease. 

Dr. Yang received his bachelor’s and master’s degrees from Stanford University and his medical degree from the University of Pennsylvania School of Medicine. He completed his internal medicine residency and fellowships in cardiovascular disease and advanced cardiac imaging at Stanford University School of Medicine. Prior to joining the faculty at UW Medicine, he was a clinical instructor and physician-scientist at Stanford. 

Dr. Yang has been on the faculty at UW Medicine since 2007 and is actively involved with the teaching of medical students, residents and fellows. He is a fellow of the American College of Cardiology and is board certified in internal medicine and cardiovascular disease. Dr. Yang’s personal interests include food, wine, golf, travel, and watching soccer.

Gina Price Lundberg MD FACC FAHA is an Associate Professor of Medicine at Emory University School of Medicine and has served as the Clinical Director of the Emory Women’s Heart Center since it was founded in 2013. She is a Preventive Cardiologist and specializes in heart disease in women, lipid abnormalities and cardiovascular risk reduction. She founded the first women’s heart prevention program in the state of Georgia in 1998. Dr Lundberg’s service at Emory University includes improving outcomes for women with cardiovascular disease but also improving gender equity for women in cardiology and encouraging more women to choose cardiology for their careers. She attended the Medical College of Georgia at Augusta University and trained in Internal Medicine at Atlanta Medical Center. Her cardiology fellowship was at Rush University in Chicago. She is active with the ACC, AHA, and NLA. She is the Chair-elect for the ACC Women in Cardiology Leadership Council and is the co-chair for the WIC Communications and Social Media Committee. She is the Co-chair for the NLA Social Media and Communications committee and the co-Chair for NLA DE&I Committee. She serves on the AHA Clinical Cardiology Communications and Social Media committee and the AHA Familial Hypercholesterolemia and Hyperlipidemia working group. And she serves as the Social Media Supervisor for JACC Case Reports.

Steven Nissen, MD, is Chief Academic Officer, Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute, and holds the Lewis and Patricia Dickey Chair in Cardiovascular Medicine. Dr. Nissen has more than 35 years of experience as a physician. He is world-renowned for his work as a cardiologist, patient advocate and researcher. Equally as significant is his pioneering work in IVUS technology and its use in patients with atherosclerosis. Dr. Nissen has written more than 400 journal articles and 60 book chapters, including many published in the New England Journal of Medicine and the Journal of the American Medical Association. In recent years, he has also written on the subject of drug safety and was the author of manuscripts highlighting concerns about medications such as Vioxx™, Avandia™, and muraglitazar. He is heavily involved with the American College of Cardiology (ACC), serving as President from March 2006 to March 2007, a member of the ACC Executive Committee from 2004 to 2008, and spending 10 years as a member of the organization’s Board of Trustees. In addition, Dr. Nissen has served several terms on the Program Committee for the ACC Annual Scientific Sessions. In his leisure time, Dr. Nissen likes to bicycle whenever possible. He is also an advanced amateur photographer.

Dr. Mahmoud Al Rifai earned his medical degree from American University of Beirut
and M.P.H. from Johns Hopkins Bloomberg School of Public Health. He completed his internal medicine residency training at University of Kansas – Wichita where he also completed a chief residency year. His career interests include academic cardiology, imaging, risk prediction, cardiovascular disease prevention and his hobbies include tennis, healthy lifestyle, reading, and coffee making.

Dr. Anum Saeed is a Clinical Instructor/Postdoctoral Associate at the University of Pittsburgh and cardiologist at UPMC. She completed her general cardiology fellowship from UPMC in June 2021 and an Atherosclerosis & Lipidology fellowship from Baylor College of Medicine in 2018. Her research focuses on studying lipids and atherosclerosis in cardiovascular disease and dementia prevention.


Jones WS, Mulder H, Wruck LM, et al., on behalf of the ADAPTABLE Team. Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease. N Engl J Med 2021; 384:1981-1990

Nicholls SJ, Lincoff AM, Garcia M, et al. Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial. JAMA. 2020;324(22):2268–2280. doi:10.1001/jama.2020.22258

Production Team

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