Targeting Hypertriglyceridemia to Mitigate Cardiovascular Risk: A Review

A causal relationship between elevated triglycerides and cardiovascular disease is controversial, as trials of triglyceride-lowering treatments have not shown significant impact on cardiovascular outcomes. However, hypertriglyceridemia is associated with atherogenesis and risk for acute cardiovascular events that persist despite optimal statin treatment. Although most trials of triglyceride-lowering treatments have been negative, in trials of niacin and fibrates, subgroup analyses in patients with higher baseline triglycerides and lower HDL-C levels suggest reduced incidence of cardiovascular endpoints. The REDUCE-IT trial demonstrated that addition of purified prescription eicosapentaenoic acid (icosapent ethyl) 4 g/day in high-risk patients with triglyceride levels 135-499 mg/dL and optimized statin treatment significantly reduced cardiovascular events versus placebo (hazard ratio 0.75; 95% confidence interval 0.68-0.83; P<0.001). Benefit was seen regardless of baseline and on-treatment triglyceride levels, suggesting that other effects of eicosapentaenoic acid besides triglyceride reduction may have played a role.