title: Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.
abstract: BACKGROUND
  Epidemiological and clinical evidence suggests that an increased intake of long-chain n-3 fatty acids protects against mortality from coronary artery disease. We aimed to test the hypothesis that long-term use of eicosapentaenoic acid (EPA) is effective for prevention of major coronary events in hypercholesterolaemic patients in Japan who consume a large amount of fish.
  
  
  METHODS
  18 645 patients with a total cholesterol of 6.5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999. Patients were randomly assigned to receive either 1800 mg of EPA daily with statin (EPA group; n=9326) or statin only (controls; n=9319) with a 5-year follow-up. The primary endpoint was any major coronary event, including sudden cardiac death, fatal and non-fatal myocardial infarction, and other non-fatal events including unstable angina pectoris, angioplasty, stenting, or coronary artery bypass grafting. Analysis was by intention-to-treat. The study was registered at ClinicalTrials.gov, number NCT00231738.
  
  
  RESULTS
  At mean follow-up of 4.6 years, we detected the primary endpoint in 262 (2.8%) patients in the EPA group and 324 (3.5%) in controls-a 19% relative reduction in major coronary events (p=0.011). Post-treatment LDL cholesterol concentrations decreased 25%, from 4.7 mmol/L in both groups. Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events. Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group. Sudden cardiac death and coronary death did not differ between groups. In patients with a history of coronary artery disease who were given EPA treatment, major coronary events were reduced by 19% (secondary prevention subgroup: 158 [8.7%] in the EPA group vs 197 [10.7%] in the control group; p=0.048). In patients with no history of coronary artery disease, EPA treatment reduced major coronary events by 18%, but this finding was not significant (104 [1.4%] in the EPA group vs 127 [1.7%] in the control group; p=0.132).
  
  
  CONCLUSIONS
  EPA is a promising treatment for prevention of major coronary events, and especially non-fatal coronary events, in Japanese hypercholesterolaemic patients.
authors.affiliation: Kobe University, Kobe, Japan. yokoyama@med.kobe-u.ac.jp
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Hideki
authors.initials: H
authors.lastname: Origasa
authors.forename: Masunori
authors.initials: M
authors.lastname: Matsuzaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oikawa
authors.forename: Jun
authors.initials: J
authors.lastname: Sasaki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hishida
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Itakura
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Akira
authors.initials: A
authors.lastname: Kitabatake
authors.forename: Noriaki
authors.initials: N
authors.lastname: Nakaya
authors.forename: Toshiie
authors.initials: T
authors.lastname: Sakata
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Shimada
authors.forename: Kunio
authors.initials: K
authors.lastname: Shirato
mesh_terms: D000328:Adult; D000368:Aged; D003327:Coronary Disease / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D004032:Diet; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications; D007564:Japan; D008297:Male; D008875:Middle Aged
chemical_list: D015118:Eicosapentaenoic Acid