REDUCE-IT: Does Icosapent Ethyl Represent New Pathway For Reducing CV Risk?

In what could represent a new pathway for cardiovascular risk reduction, findings from the REDUCE-IT trial show icosapent ethyl (2 g/twice daily) significantly reduced the risk of major ischemic events, including cardiovascular death, in patients with elevated triglyceride levels despite statin therapy. The findings were presented Nov. 10 at AHA 2018 in Chicago, IL, and simultaneously published in the New England Journal of Medicine.

Researchers, led by Deepak L. Bhatt, MD, MPH, FACC, randomized 8,179 patients with established cardiovascular disease or with diabetes and other factors to receive either 2 g of icosapent ethyl twice daily or placebo. All patients were on statin therapy and had a fasting triglyceride level from 135 to 499 mg per deciliter and an LDL-C level from 41 to 100 mg per deciliter. Median follow-up was 4.9 years. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, coronary revascularization or unstable angina. A secondary endpoint was a composite of cardiovascular death, nonfatal MI or nonfatal stroke.

Results showed a primary endpoint event occurred in 17.2 percent of patients in the icosapent ethyl group compared with 22.0 percent in the placebo group. Secondary endpoint risk was also lower by 26 percent in the icosapent ethyl group compared with the placebo group. Prespecified hierarchical testing of other secondary endpoints revealed, in part, a 20 percent lower risk of cardiovascular death, the authors said.

In other findings, overall rates of adverse events were similar in both groups, according to the authors. However, serious adverse events related to bleeding, as well as rates of hospitalization for atrial fibrillation or flutter were higher in the icosapent ethyl group compared with the placebo group, although in both cases rates were low. Over the course of the follow-up period, researchers noted the median change in triglyceride level from baseline to one year was a decrease of 18.3 percent in the icosapent ethyl group compared with an increase of 2.2 percent in the placebo group. The median reduction from baseline was 19.7 percent greater in the icosapent ethyl group compared with placebo. Additionally, while the median change in LDL-C levels from baseline increased in both groups, there was a 6.6 percent lower increase in the icosapent ethyl group compared to placebo (3.1 percent vs. 10.2 percent).

Bhatt noted certain limitations to the trial, including the relatively limited use of ezetimibe and PCSK9 inhibitors at the time the trial was designed. However, based on subgroup analyses, he and his colleagues did not observe a differential benefit for patients taking ezetimibe. Further studies to understand the mechanisms responsible for the benefit of icosapent ethyl are needed. Ongoing trials of moderate-to-high doses of pure EPA ethyl ester will also provide further information on the effects of these agents, according to the authors.

Keywords: AHA18, AHA Annual Scientific Sessions, Hypertriglyceridemia, Metabolic Diseases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Fatty Acids, Omega-3

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