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N Engl J Med. 2018 Nov 10. doi: 10.1056/NEJMoa1812792. [Epub ahead of print]

Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia.

Author information

1
From Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston (D.L.B.); FACT (French Alliance for Cardiovascular Trials), Département Hospitalo-Universitaire FIRE (Fibrose, Inflammation, and Remodeling), Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Université Paris-Diderot, INSERM Unité 1148, Paris (P.G.S.); National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London (P.G.S.); the Department of Medicine, University of Maryland School of Medicine, Baltimore (M.M.); the Utah Lipid Center, Salt Lake City (E.A.B.); the Office of Health Promotion and Disease Prevention, Department of Medicine, Emory University School of Medicine, Atlanta (T.A.J.); Amarin Pharma, Bedminster, NJ (S.B.K., R.T.D.J., R.A.J., L.J., C.G.); Montreal Heart Institute, Université de Montréal, Montreal (J.-C.T.); and the Department of Medicine, Baylor College of Medicine, and the Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston (C.M.B.).

Abstract

BACKGROUND:

Patients with elevated triglyceride levels are at increased risk for ischemic events. Icosapent ethyl, a highly purified eicosapentaenoic acid ethyl ester, lowers triglyceride levels, but data are needed to determine its effects on ischemic events.

METHODS:

We performed a multicenter, randomized, double-blind, placebo-controlled trial involving patients with established cardiovascular disease or with diabetes and other risk factors, who had been receiving statin therapy and who had a fasting triglyceride level of 135 to 499 mg per deciliter (1.52 to 5.63 mmol per liter) and a low-density lipoprotein cholesterol level of 41 to 100 mg per deciliter (1.06 to 2.59 mmol per liter). The patients were randomly assigned to receive 2 g of icosapent ethyl twice daily (total daily dose, 4 g) or placebo. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary end point was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.

RESULTS:

A total of 8179 patients were enrolled (70.7% for secondary prevention of cardiovascular events) and were followed for a median of 4.9 years. A primary end-point event occurred in 17.2% of the patients in the icosapent ethyl group, as compared with 22.0% of the patients in the placebo group (hazard ratio, 0.75; 95% confidence interval [CI], 0.68 to 0.83; P<0.001); the corresponding rates of the key secondary end point were 11.2% and 14.8% (hazard ratio, 0.74; 95% CI, 0.65 to 0.83; P<0.001). The rates of additional ischemic end points, as assessed according to a prespecified hierarchical schema, 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). A larger percentage of patients in the icosapent ethyl group than in the placebo group were hospitalized for atrial fibrillation or flutter (3.1% vs. 2.1%, P=0.004). Serious bleeding events occurred in 2.7% of the patients in the icosapent ethyl group and in 2.1% in the placebo group (P=0.06).

CONCLUSIONS:

Among patients with elevated triglyceride levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower among those who received 2 g of icosapent ethyl twice daily than among those who received placebo. (Funded by Amarin Pharma; REDUCE-IT ClinicalTrials.gov number, NCT01492361 .).

PMID:
30415628
DOI:
10.1056/NEJMoa1812792
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