Lead investigator of REDUCE-IT trials discusses the impact of trial results and what that means for EPA-based treatments going forward.
With results of the REDUCE-IT trial demonstrating the efficacy of icosapent ethyl (Vascepa)— a pure EPA product — many expect the New Drug Application for cardiovascular risk reduction in patients with statin managed LDL-C cholesterol to receive approval from the US Food and Drug Administration in September. Additionally, the American Diabetes Association recently added the potential treatment to their Living Standards of Care to reduce cardiovascular risk in patients with diabetes and atherosclerotic cardiovascular disease.
With icosapent ethyl receiving Priority Review designation from the FDA and being added to treatment guidelines — even before becoming officially approved — its impact on clinical practice is already evident. Yet, it’s success has also prompted questions into the use of other EPA-based and omega-3 supplements or therapies for treatment of the same conditions.
MD Magazine® recently sat down with REDUCE-IT trial lead investigator Deepak Bhatt, MD, MPH, executive director of Interventional Cardiovascular Programs at Brigham and Women's Hospital and professor of medicine at Harvard Medical School, to get his take on icosapent ethyl’s impact and what that means for EPA-based drugs going forward.
MD Mag: How will REDUCE-IT results impact clinical practice and what does that mean for the future of EPA-based drugs going forward?
Bhatt: My hope is that the trial results of REDUCE-IT will be viewed as practice-changing. Certainly, we saw large degrees of benefit across a variety of different endpoints including a 20% risk reduction in cardiovascular death that was statistically significant — also, significant reductions in myocardial infarction, stroke, hospitalization for unstable angina, revascularization procedures. So, the number of events prevented — in terms of the population treated — was really quite substantial and, therefore, I think physicians will view the results as practice changing once they become familiar with the trial results.
Now, whether the results apply to icosapent ethyl — the prescription medication that we studied — or whether they would be generalized to other different sorts of triglyceride lowering compounds or omega-3 fatty acids is a question that I'm commonly asked and I think the results of the trial apply to the drug we studied, which was icosapent ethyl 2 grams twice a day — so, a total of 4 grams a day of that highly purified by eicosapentaenoic acid. That is very different from studies say the ASCEND trial or the VITAL trial that also examined Omega-3s at a lower dose — a gram a day — and mixed preparations of DHA and EPA, not a pure EPA at a high dose as we studied. So, I don't think the results of our trial could be applied to those drugs, which, in fact, have been shown to be negative in terms of trials such as VITAL and ASCEND and meta analyses of some of the older trials.
So, the results that we saw, which I think are quite impressive in terms of magnitude of benefit, really shouldn't be extrapolated to other compounds either other prescription compounds that may lower triglycerides such as the ones I mentioned or fibrates or niacin and certainly shouldn't be extrapolated to over-the-counter supplements, which are not closely regulated and have variable degrees of EPA and DHA and other substances and saturated fats and so on in them.
So, really the results should be applied to icosapent ethyl — and this is a position as well that in the most recent update to the guidelines the American Diabetes Association agreed with; that is, they gave a level A recommendation —their highest level of evidence — to use of icosapent ethyl in primary and secondary prevention type patients with elevated triglycerides in the range I mentioned of 135 to 500 despite therapy with statins. So, that's really the target population for icosapent ethyl and those ADA 2019 update guidelines said that the results really shouldn't be applied to supplements or niacin or fibrates. In fact, they say those different compounds shouldn't be used with statin therapy because there's no evidence supporting their use.