Newswise – Sunday, May 16, 2021 in Cleveland: A secondary analysis of the Cleveland Clinic’s STRENGTH study found that high levels of eicosapentaenoic acid (EPA), an omega-3 fatty acid, were of no benefit to patients at high risk for cardiovascular events.
The results of the secondary analysis were presented today during a Late Breaking Science Session at the 70th Annual Scientific Session of the American College of Cardiology and also published online on JAMA Cardiology.
In the study, patients who achieved the highest EPA levels had similar rates of serious cardiovascular adverse events as those who took a corn oil placebo. The EPA was measured 12 months after starting 4 g of a prescription omega-3 product every day.
“Our analysis shows no evidence that high EPA levels are of cardiovascular benefit,” said Dr. Steven Nissen, Chief Academic Officer of the Cardiovascular and Thoracic Institute at the Cleveland Clinic, and the lead author of the study. “Previous studies have shown that fish oil supplements or ikosapentes ethyl help lower triglycerides in people with very high levels of triglycerides. According to current knowledge, however, the overall cardiovascular risk for patients is not reduced. ”
In the STRENGTH study, 13,078 patients were randomized to receive a daily supplement with high-dose omega-3 fatty acids or placebo (corn oil). The high-dose omega-3 fatty acid drug used in the study – not available over the counter – did not significantly reduce serious adverse cardiovascular events compared to corn oil. The study was terminated prematurely because there was no significant difference between the groups in the primary outcome.
A previous clinical study published in 2018 found that the use of icosapent Ethyl, a highly purified EPA formulation, significantly reduced cardiovascular events and cardiovascular death in high-risk patients compared to a mineral oil placebo. However, according to the authors of STRENGTH, the study was controversial as mineral oil had adverse effects on cholesterol and markers of inflammation, which may have exaggerated icosapent Ethyl’s obvious benefits.
The secondary analysis of the STRENGTH study looked at a subset of 10,382 patients with available omega-3 fatty acid levels, with 5,175 receiving omega-3 carboxylic acid and 5,207 receiving the corn oil placebo. Serious cardiovascular adverse events occurred in 11.1% of patients treated with fish oil and 11% of patients in the placebo group. Overall, this group of patients was 62.5 years old, an average of one third were women and another third had diabetes.
The researchers grouped the patients into thirds based on how much EPA and DHA were in their blood at baseline and again a year later. They found no difference in serious adverse events in patients in the upper third of EPA and DHA levels after one year compared to patients treated with corn oil. Sensitivity analyzes were also performed on changes in EPA and DHA plasma levels, EPA and DHA levels in red blood cells, and the subgroups of primary and secondary prevention. No treatment effects were found here either.
The study’s authors add that both the original study and secondary analysis indicated that omega-3 fatty acid administration posed risks. “2.2% of the patients in the fish oil group had an increase in the incidence of atrial fibrillation compared to 1.3% of the patients who took corn oil,” said Dr. Michael Lincoff, vice chairman of the cardiovascular medicine department and director of C5Research at the Cleveland Clinic and the second author of STRENGTH.
The original STRENGTH study was funded by AstraZeneca. Dr. Nissen has worked as a consultant for many pharmaceutical companies and led clinical studies for Amgen, AstraZeneca, Cerenis, Eli Lilly, Novartis, Novo Nordisk, The Medicines Company, Orexigen, Takeda and Pfizer. However, he does not accept any fees, consulting fees or other remuneration from commercial companies. Dr. Lincoff has received research grants from Amgen, Astra Zeneca, CSL Behring, Esperion, Eli Lilly and Novartis and has acted as a consultant to Novo Nordisk and Eli Lilly.
The study was coordinated by the Cleveland Clinic Coordinating Center for Clinical Research (C5Research). The protocol was developed by members of the independent academic steering committee in collaboration with AstraZeneca, the sponsor of the study.
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The Cleveland Clinic, now in its centenary, is a multi-specialty, nonprofit academic medical center that combines clinical and hospital care with research and teaching. Located in Cleveland, Ohio, the company was founded in 1921 by four renowned physicians with a vision to deliver superior patient care based on the principles of collaboration, compassion and innovation. The Cleveland Clinic has made many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. US News & World Report consistently names the Cleveland Clinic one of the best hospitals in the country in its annual America’s Best Hospitals survey. The Cleveland Clinic’s 70,800 employees worldwide include more than 4,660 employed physicians and researchers, and 18,500 registered nurses and advanced practice providers representing 140 medical specialties and subspecialties. The Cleveland Clinic is a 6,500 bed healthcare system that includes a 173-acre main campus near downtown Cleveland, 19 hospitals, more than 220 outpatient facilities, and locations in southeast Florida. Las Vegas, Nevada; Toronto Canada; Abu Dhabi, United Arab Emirates; and London, England. In 2020, there were 8.7 million outpatient visits, 273,000 hospital admissions and observations, and 217,000 surgical cases across the Cleveland Clinic healthcare system. Patients came for treatment from all states and 185 countries. Visit us at clevelandclinic.org. Follow us on twitter.com/ClevelandClinic. For news and resources, visit newsroom.clevelandclinic.org.
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