The REDUCE-IT Trial and CVD Prevention


An overview of the REDUCE-IT trial of icosapent ethyl for the management of triglycerides and prevention of cardiovascular events.

Dhiren Patel, PharmD, CDCES, BC-ADM, BCACP: So, up until now, we’ve talked a lot about LDL [low-density lipoprotein] and some of the fluids that we have there. Dr Bhatt, I would love it if you can maybe kick off and talk a little bit about triglycerides. It’s not something that we’ve focused a lot of our attention on until recently. You led the REDUCE-IT [Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia] trial, and Dr Busch, I think you were 1 of the sites there. So very rarely do I get to hear it from the primary source, but maybe if you could just talk a little bit about the REDUCE-IT trial. And then what the quick adoption by medical guidelines and societies all over the world and what that now means from a clinical practice standpoint.

Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC: Absolutely. I think that it’s a great question. It’s an important aspect of cardiovascular risk reduction. We’ve been focusing on LDL and, indeed, the world of cardiovascular risk reduction has been very LDL-centric. Rightly so, lots of progress there. But there are other cardiovascular risk factors even in the lipid domain, and triglycerides are really 1 of them. And in different years, triglycerides have been in, they’ve been out, but they’re back in again as a risk factor. And that’s based on a number of different lines of evidence, lots of science now supporting the triglycerides, much like LDL are directly causal or directly atherogenic. Though, to be scientifically precise, it’s really triglyceride-rich lipoproteins more than just what we measure in terms of triglycerides, per se. But regardless, they do appear to have an independent effect on cardiovascular risk above and beyond LDL cholesterol. How to modulate that risk has also been a source of contention and debate. In the REDUCE-IT trial, we studied patients with elevated triglycerides. I should point out that that was just sort of something we did because a number of members of the steering committee were very lipid focused. I must say, personally, I didn’t really think there needed to be a triglyceride entry criterion in the trial, but ultimately, there was. Patients had to have elevated triglycerides above about 135 or so milligrams per deciliter, and less than 500 milligrams per deciliter. So, in that range, we enrolled patients, about 70% of them were stable secondary prevention. By that, I mean atherosclerosis and their coronary or peripheral or cerebral vasculature. But another 30%, I’ll say are high-risk primary prevention, but specifically were those patients with diabetes and at least 1 additional cardiovascular risk factor. So that was the overall population, 8000 patients followed for an average of about 5 years. And we randomized them to icosapent ethyl [Vascepa] or to placebo.

And icosapent ethyl is a medicine that had already been approved for triglyceride reduction, based on a trial called MARINE [Marine Omega-3 Supplementation and Cardiovascular Disease: An Updated Meta-Analysis of 13 Randomized Controlled Trials Involving 127 477 Participants] for people with really high triglycerides, over 500, to hopefully prevent pancreatitis. But we were studying it in patients with a lower level of triglycerides in that, not to see if it will prevent pancreatitis, but rather to see if it reduced cardiovascular events. Just to say a quick word about what icosapent ethyl is, it’s an omega-3 fatty acid, but specifically a highly purified ethyl ester of EPA, or eicosapentaenoic acid, which is 1 of many different omega-3 fatty acids. It’s a prescription medicine, not a supplement. And it is pure EPA, unlike most of the different prescription or supplements out there of omega-3s that are mixtures of EPA and docosahexaenoic acid, DHA, and other fatty acids. So pure ethyl ester of EPA. And what we found then with this drug was a significant reduction in cardiovascular events, about a 25% reduction in ischemic events, specifically a 26% reduction in death from cardiovascular causes, heart attacks, stroke, so really important cardiovascular end points with large risk reductions. So that’s the overall trial. And, it was, again, over 8000 patients, I think very representative of clinical practice, in fact. Dr Busch was 1 of the leading enrollers of patients in the trial, and I think it reflects real world practice, that these weren’t some super carefully selected patients. These were just patients at high cardiovascular risk that happened to have elevated triglycerides. Certainly, the trial does support measurement of triglycerides to identify patients who then, for the U.S. label, would be candidates for icosapent ethyl to reduce cardiovascular risk.

Transcript edited for clarity.

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