Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia (REDUCE-IT)

After decades of disappointing fish-oil trials, REDUCE-IT was the study that finally showed an omega-3 product preventing cardiovascular events — and it matters as much for its caveats as its success.

The trial gave 4 grams daily of icosapent ethyl, a purified form of the omega-3 EPA, to statin-treated patients with elevated triglycerides and high cardiovascular risk. The result was a 25 percent relative reduction in major cardiovascular events, including cardiovascular death, with a number-needed-to-treat of 21 over about five years — a clinically substantial benefit on top of well-managed statin therapy.

The crucial qualifier is specificity. This was a particular high-dose, purified-EPA formulation, and its success should not be read as endorsement of over-the-counter fish-oil capsules or mixed EPA/DHA products, which have repeatedly failed in trials. There was also debate about whether the mineral-oil placebo may have slightly exaggerated the effect. Still, REDUCE-IT established a genuine role for one specific therapy in residual triglyceride-related risk.

We rate the evidence very strong. It is a large, rigorous, placebo-controlled outcomes trial that changed guidelines — with the firm proviso that its benefit belongs to this drug and dose, not to omega-3s in general.