News Release

PHILADELPHIA – Twice-daily doses of a purified, prescription-strength form of the omega-3 fatty acid EPA (eicosapentaenoic acid) may substantially lower the rates of heart attacks and strokes in current and former smokers with high cardiovascular disease risk, suggests a study led by researchers at the Perelman School of Medicine at the University of Pennsylvania and the Corporal Michael J Crescenz VA Medical Center.

The study, presented August 28 at the European Society of Cardiology Congress in Barcelona and published in the European Heart Journal—Cardiovascular Pharmacotherapy, analyzed results from an earlier, landmark clinical trial, the REDUCE-IT study, in adults at high risk for heart attacks and other cardiovascular events.

The REDUCE-IT study had found, compared to a placebo group, a 25 percent reduction in the rate of having a heart attack, stroke, or other serious cardiovascular event in individuals treated with icosapent ethyl (IPE), essentially a pure form of EPA. The new analysis focused on the current and former smokers in the REDUCE-IT study, and again found a substantial—23 percent—reduction in the rate of having a cardiovascular event.

“We always want our patients who are smokers to quit, and IPE shouldn’t be seen as a substitute for quitting smoking,” said study lead author Michael Miller, MD, vice chair of Medicine at the Hospital of the University of Pennsylvania and chief of Medicine at the Corporal Michael J Crescenz VA Medical Center. “But it is something for high-risk individuals and their doctors to consider as another way of lowering cardiovascular risk.”

EPA is one of the omega-3 fatty acids—found in coldwater fish, for example—that people commonly use as dietary supplements, in the hope of reducing their risks of atherosclerosis, heart attacks, and strokes. In sufficient doses, omega-3 fatty acids can inhibit inflammation, reduce blood pressure, lower bloodstream levels of fats called triglycerides, and reduce the stickiness of the platelets that cause blood clots.

Prior studies have suggested, however, that EPA and its omega-3 cousins don’t have clinically significant effects in high-risk individuals when administered at the doses found in common dietary supplements, which are not regulated as drugs and typically contain many non-omega-3 ingredients. Thus, the REDUCE-IT study used a highly purified EPA formulation IPE, and at high doses of two grams twice per day with meals. The success of that trial led to the U.S. Food and Drug Administration’s 2019 approval of the IPE product used in the study (brand name Vascepa) for preventing cardiovascular events in certain high-risk individuals.

Miller was one of the lead investigators for the REDUCE-IT study. He and other REDUCE-IT researchers performed the new analysis to gauge the effect of IPE on the current and former smokers in the REDUCE-IT study. Current or past cigarette smoking is known to be a major risk factor for cardiovascular disease. Indeed, they found that placebo-treated current smokers in the REDUCE-IT study had a much higher rate of cardiovascular events over five years (30.4 percent) compared to placebo-treated nonsmokers (25.7 percent). But the IPE-treated current smokers had only a 23.8 percent rate of cardiovascular events.

Although the current/former smokers in the REDUCE-IT study made up about 60 percent of the total study population, the smokers-only analysis is not one that was planned before the study. It is thus considered an exploratory or “post-hoc” analysis that, in principle, should be confirmed with a clinical trial specifically designed that way in advance. However, the results point strongly to the possibility that IPE or similar EPA formulations can meaningfully reduce cardiovascular risk in current and former smokers, perhaps even when they aren’t in the high-risk category used for REDUCE-IT, as future studies may determine.

“The promising results from this exploratory study suggest that it would be worthwhile to do a formal clinical trial of IPE as a preventive of cardiovascular events in current and former smokers,” Miller said. “Until we conduct such a trial, doctors could consider prescribing IPE to current and former smokers who fit the high-risk criteria of the REDUCE-IT study.”

Editor’s Note: REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl—Intervention Trial) was sponsored by Amarin Pharma, Inc., for which Miller services as a scientific advisor. 


Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.

The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.

The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is an $11.1 billion enterprise powered by more than 49,000 talented faculty and staff.

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