Effects of eicosapentaenoic acid on cardiovascular events in Japanese patients with hypercholesterolemia: rationale, design, and baseline characteristics of the Japan EPA Lipid Intervention Study (JELIS)

Am Heart J. 2003 Oct;146(4):613-20. doi: 10.1016/S0002-8703(03)00367-3.

Abstract

Hypothesis: The principle aim of the current study is to test the hypothesis that the long-term use of highly purified EPA (eicosapentaenoic acid: 1800 mg/day), in addition to HMG-CoA reductase inhibitor, is effective in preventing cardiovascular events in Japanese patients with hypercholesterolemia.

Background: Epidemiological and clinical evidence suggest that intake of long-chain polyunsaturated n-3 fatty acids (PUFAs), which are abundant in fish, might have a significant role in the prevention of coronary artery disease, as marine PUFAs have multiple biological functions through lipid-dependent and lipid-independent mechanisms.

Methods: The Japan EPA Lipid Intervention Study (JELIS) is a prospective, randomized, open-label, blinded end point trial including both primary and secondary prevention strata, with a maximum follow-up of 5 years. Its main purpose is to examine the clinical effectiveness of EPA oil given as an additional treatment to patients taking HMG-CoA reductase inhibitors for hypercholesterolemia. A primary end point is major coronary events: sudden cardiac death, fatal and nonfatal myocardial infarction, and unstable angina pectoris including hospitalization for documented ischemic episodes, and events of angioplasty/stenting or coronary artery bypass grafting. Secondary end points include all-cause mortality, stroke, peripheral artery disease, and cancer. Baseline study composition comprises 15,000 participants (4204 men and 10,796 women) in the primary prevention stratum and 3645 (1656 men and 1989 women) in the secondary stratum. The minimum age is 40 years for men, women are required to be postmenopausal, and all patients must be < or =75 years of age. The mean age of participants is 61 years, and 69% are female. The schedule for plasma fatty acid composition measurement is as follows: at baseline, at 6 month, and yearly thereafter. The mean baseline total and low-density lipoprotein cholesterol levels were 275 mg/dL (7.1 mmol/L) and 180 mg/dL (4.6 mmol/L).

Results: Results are expected in 2005.

Conclusion: JELIS is a large clinical trial that will evaluate whether EPA can make an additional improvement in mortality and morbidity of coronary artery disease beyond that of HMG-CoA reductase inhibitor treatment.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angina, Unstable / prevention & control
  • Anticholesteremic Agents / therapeutic use
  • Chemotherapy, Adjuvant
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / prevention & control*
  • Death, Sudden, Cardiac
  • Eicosapentaenoic Acid
  • Fatty Acids, Unsaturated / therapeutic use*
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypercholesterolemia / drug therapy*
  • Japan
  • Male
  • Middle Aged
  • Myocardial Infarction / prevention & control
  • Pravastatin / therapeutic use
  • Prospective Studies
  • Simvastatin / therapeutic use

Substances

  • Anticholesteremic Agents
  • Fatty Acids, Unsaturated
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Eicosapentaenoic Acid
  • Simvastatin
  • Pravastatin