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Japan EPA Lipid Intervention Study - JELIS
Description:
The goal of the trial was to evaluate treatment with the fish oil supplement eicosapentaenoic acid (EPA) in addition to statin therapy compared with statin therapy alone among patients with hypercholesterolemia.
Study Design
Study Design:
Patients Enrolled: 18645
Mean Follow Up: Mean follow-up 4.6 years
Mean Patient Age: Mean age 61 years
Female: 68
Patient Populations:
Total cholesterol ≥250 mg/dl; men age 40-75 years or post-menopausal women up to age 75 years
Primary Endpoints:
Major adverse coronary events (MACE), defined as sudden cardiac death, unstable angina, myocardial infarction, or revavscularization
Drug/Procedures Used:
The trial was conducted in Japan. Patients were randomized in an open-label manner to treatment with EPA (1,800 mg/day; n=9,326) in addition to statin therapy or to statin therapy alone (n=9,319). Statin therapy was either pravastatin (10 mg/day) or simvastatin (5 mg/day).
Principal Findings:
Baseline characteristics were well balanced between the treatment groups, wtih 16% diabetics, 20% having coronary artery disease and 19% smokers. Mean total cholesterol at baseline was 275 mg/dL and mean LDL was 182 mg/dL. In both groups, total cholesterol was reduced 19% from baseline and LDL was reduced 25% from baseline.
The primary endpoint of MACE at mean 4.6 year follow-up was significantly lower in the EPA plus statin group compared with the statin alone group (2.8% vs 3.5%, hazard ratio [HR] 0.81, p=0.011). Among the components of the composite endpoint, the EPA plus statin group had lower rates of unstable angina (1.6% vs 2.1%, HR 0.76, p=0.014) and a trend toward lower rates of nonfatal MI (0.7% vs 0.9%, p=0.086) and revascularization (2.1% vs 2.4%, p=0.135) with no difference in sudden cardiac death (0.2% each) or fatal MI (0.1% vs 0.2%, p=NS).
Among the subgroup of patients without prior coronary artery disease (n=14,981), i.e., the primary prevention cohort, the primary endpoint was non-significantly lower in the EPA plus statin group compared with the statin alone group (1.4% vs 1.7%, HR 0.82, p=0.132). Among the subgroup of patients with prior coronary artery disease (n=3,664), i.e., the secondary prevention cohort, the primary endpoint was significantly lower in the EPA plus statin group (8.7% vs 10.7%, HR 0.81, p=0.048). Adverse events were slightly higher in the EPA plus statin group (25.3% vs 21.7%, p<0.0001), including GI disorders (3.8% vs 1.7%, p<0.0001).
Interpretation:
Among patients with hypercholesterolemia, treatment with the fish oil supplement EPA in addition to statin therapy was associated with a reduction in the primary composite endpoint at a mean of 4.6 years compared with statin therapy alone.
Prior epidemiologic studies have shown that diets high in fatty acids found in fish are associated with lower rates of coronary heart disease and mortality. However, randomized trials using fish oil supplements have shown mixed results, and were often small in size. The present study, which did show a benefit with the fish oil supplement EPA, was well powered to detect a difference in clincal events. The reduction in MACE with EPA on top of statin therapy was independent of the reduction in total cholesterol and LDL, which was lowered in a similar amount in both groups. It should be noted that the dose of EPA used in the present study (1,800 mg/day) is quite high, and adverse events were higher in the combination group than in the statin therapy alone group.
References:
Yokoyama M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007 Mar 31;369(9567):1090-8.
Presented by Dr. Mitsuhiro Yokoyama at the American Heart Association Scientific Session, Dallas, Texas, November 2005.
Keywords: Coronary Artery Disease, Follow-Up Studies, Cholesterol, LDL, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Simvastatin, Hypercholesterolemia, Eicosapentaenoic Acid, Primary Prevention, Secondary Prevention, Pravastatin, Diet, Diabetes Mellitus, Death, Sudden, Cardiac
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