Mechanistic Insights from REDUCE-IT STRENGTHen the Case Against Triglyceride Lowering as a Strategy for Cardiovascular Disease Risk Reduction.

Abstract

Elevated triglyceride (TG) levels have been linked to residual atherosclerotic cardiovascular risk in patients with controlled low-density lipoprotein cholesterol (LDL-C). However, outcome trials testing TG-lowering agents have failed to demonstrate cardiovascular risk reduction in statin-treated subjects. One such example is the recent STRENGTH trial, which tested mixed omega fatty acids (n3-FAs, 4g/d) in high-risk patients with elevated TGs. Similar to trials using fibrates and niacin, STRENGTH failed despite effective TG-lowering. Results from these studies have contributed to skepticism about the use of TG-lowering therapy for cardiovascular risk. But new mechanistic insights are provided by the REDUCE-IT trial that used icosapent ethyl (IPE), a purified formulation of the n3-FA eicosapentaenoic acid (EPA). In high-risk patients, IPE reduced a composite of cardiovascular events (25%, P<0.001) in a manner not predicted by TG-lowering. Benefits with IPE appear linked to broad pleiotropic actions associated with on-treatment EPA levels. These studies indicate that while TGs are a potential biomarker of cardiovascular risk, there is no evidence that TG-lowering itself is an effective strategy for reducing such risk.