Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.
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.
Yokoyama
Mitsuhiro
M
Kobe University, Kobe, Japan. yokoyama@med.kobe-u.ac.jp
Origasa
Hideki
H
Matsuzaki
Masunori
M
Matsuzawa
Yuji
Y
Saito
Yasushi
Y
Ishikawa
Yuichi
Y
Oikawa
Shinichi
S
Sasaki
Jun
J
Hishida
Hitoshi
H
Itakura
Hiroshige
H
Kita
Toru
T
Kitabatake
Akira
A
Nakaya
Noriaki
N
Sakata
Toshiie
T
Shimada
Kazuyuki
K
Shirato
Kunio
K
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
D015118:Eicosapentaenoic Acid