Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published January 2, 2019


Does icosapent ethyl therapy lower the risk of ischemic events in at-risk patients with hypertriglyceridemia? 

Bhatt et al. conducted the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) to evaluate the risk of cardiovascular events with icosapent ethyl versus placebo in patients with established cardiovascular disease, or with diabetes and other risk factors, who had low-density lipoprotein cholesterol levels of 41 to 100 mg per deciliter (1.06 to 2.59 mmol per liter), but elevated triglyceride levels despite statin therapy. Read the NEJM original article here

Clinical Pearls

Q: What was the Japan EPA Lipid Intervention Study?

A: In the Japan EPA Lipid Intervention Study (JELIS), 18,645 Japanese patients with hypercholesterolemia were randomly assigned to receive either low-intensity statin therapy plus 1.8 g of eicosapentaenoic acid (EPA) daily or statin therapy alone. The risk of major coronary events was significantly lower, by 19%, in the group that received EPA plus statin therapy than in the group that received statin therapy alone.

Q: What is icosapent ethyl?

A: Icosapent ethyl is a highly purified and stable EPA ethyl ester that has been shown to lower triglyceride levels and is used as an adjunct to diet in adult patients who have triglyceride levels of at least 500 mg per deciliter (5.64 mmol per liter). In addition, icosapent ethyl may have antiinflammatory, antioxidative, plaque-stabilizing, and membrane-stabilizing properties.

Morning Report Questions

Q: Does icosapent ethyl therapy lower the risk of ischemic events in at-risk patients with hypertriglyceridemia?

A: In REDUCE-IT, the risk of the primary composite end point of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina, assessed in a time-to-event analysis, was significantly lower, by 25%, among the patients who received 2 g of icosapent ethyl twice daily than among those who received placebo. In the prespecified hierarchical testing of end points, the rates of all individual and composite ischemic end points (except for death from any cause — the last secondary end point in the hierarchy) were significantly lower in the icosapent ethyl group than in the placebo group, including the rate of cardiovascular death (4.3% vs. 5.2%; hazard ratio, 0.80; 95% CI, 0.66 to 0.98; P=0.03). The rate of death from any cause was 6.7% in the icosapent ethyl group and 7.6% in the placebo group (hazard ratio, 0.87; 95% CI, 0.74 to 1.02). 

Q: Is the benefit of icosapent ethyl in REDUCE-IT explained by a reduction of triglyceride levels?

A: The observed cardiovascular benefits were similar across baseline levels of triglycerides (<150, ≥150 to <200, and ≥200 mg per deciliter). In addition, the significantly lower risk of major adverse cardiovascular events with icosapent ethyl than with placebo appeared to occur irrespective of the attained triglyceride level at 1 year (≥150 or <150 mg per deciliter), which suggests that the cardiovascular risk reduction was not associated with attainment of a more normal triglyceride level. These observations suggest that at least some of the effect of icosapent ethyl that resulted in a lower risk of ischemic events than that with placebo may be explained by metabolic effects other than a reduction of triglyceride levels. Mechanisms responsible for the benefit of icosapent ethyl observed in REDUCE-IT are currently not known.

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