New results presented at the American College of Cardiology's 68th Annual Scientific Session find a high-dose fish oil pill reduced the risk for first and future cardiovascular events among patients taking statins by 30%. The early results grabbed headlines last fall in part because researchers aren't entirely sure how the capsule works.
Amarin’s prescription omega-3 fatty acid, a high dose of a purified fish oil component, reduced by 30% the risk for first and future cardiovascular events among patients taking statins, according to results presented Monday at the American College of Cardiology’s 68th Scientific Session in New Orleans, Louisiana.
New results from REDUCE-IT, which grabbed headlines last fall at the American Heart Association (AHA) meeting, aligned with initial findings that showed the omega-3 fatty acid capsule, icosapent ethyl (Vascepa), reduced the risk of initial cardiovascular events by 25%. In this round of data, the risk of second events dropped 32%, third events, 31%; and fourth events, 48%.
According to the findings presented Monday, for every 1000 patients treated for 5 years, approximately 159 cardiovascular events would be prevented. The new results were simultaneously published in the Journal of the American College of Cardiology.
REDUCE-IT randomized 8179 patients to receive either 4 g/day of icosapent ethyl or placebo. After a median follow-up of 4.9 years, researchers knew the vital status of 99.9% of the group taking the study drug and 99.7% of those taking placebo. Primary endpoints events were cardiovascular death, nonfatal myocardial infarction (MI), coronary revascularization, and hospitalization for unstable angina; secondary endpoint events were cardiovascular death, nonfatal MI, and nonfatal stroke.
Led by Deepak Bhatt, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital, the REDUCE-IT researchers showed in this round of data that patients taking the icosapent ethyl capsule have a reduced risk of future events even if they have an initial heart attack, and even if they are taking other medications, as would be expected in a high-risk population. Virtually all the patients in the study were taking a statin, and 79% were taking at least 1 antiplatelet therapy.
Just how the capsule works remains a mystery. While supplements containing omega-3 fatty acid abound, the dose of icosapent ethyl studied is a purified eicosapentaenoic acid, or EPA. It is believed that these fatty acids work by reducing triglycerides throughout the body.
Both Bhatt, who presented the findings, and Peter Toth, MD, director of Preventive Cardiology at CGH Medical Center, who spoke on behalf of Amarin, separately told The American Journal of Managed Care® (AJMC®) that the new findings bolster the case for triglycerides as a marker of risk. Bhatt said future research will explore more biomarkers to completely explain the mechanism; he compared the situation to the early days of statins, when researchers did not fully understand all their inflammatory markers.
Plus, Toth said, “This wasn’t a trial to determine the mechanism of action.”
Some have asked if the mineral oil capsule used as the placebo in REDUCE-IT caused reactions that made icosapent ethyl seem more effective than it is. Toth replied that the study sponsors used the placebo requested by the FDA. He said physicians in clinical practice are “fascinated” by the results. “They are eager to apply the findings to the patients in their practices,” Toth said.
Two cost-effectiveness analyses are planned. One will be done by the Institute for Clinical and Economic Review and the other will be done by Bhatt’s team. AJMC® asked if some data could be problematic with payers, as results showed it can take up to 2 years for the capsule’s benefits to take full effect, but adherence starts to decline at the same point.
Bhatt said a full answer for payers will require the cost-effectiveness analysis. “But even in the absence of that, it’s pretty likely this will be cost-effective at the current price point of the drug, just because there’s a substantial reduction in ischemic events—including events from a patient’s perspective.” From a third-party payer perspective, he said, reductions in stents and bypass surgery will be convincing.
According to the website GoodRx, the current retail price for a 120-capsule supply of icosapent ethyl without insurance is between $348 and $364, but with a manufacturer’s coupon it can be purchased for $245. A statement from Amarin said most patients with insurance will have a monthly co-pay of $9.99 or less.
FDA approved icosapent ethyl in July 2012 for treatment of severe triglycerides. Amarin has announced plans to file a supplemental New Drug Application for a cardiovascular indication based on REDUCE-IT in the first quarter of 2019.
Bhatt DL, Steg PG, Miller M, et al. Effects of icosapent ethyl on total ischemic events: From REDUCE-IT [published online March 18, 209]. J Am Coll Cardiol. doi: 10.1016/j.jacc.2019.02.032.