Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS).
BACKGROUND
Japan EPA Lipid Intervention Study (JELIS) was a large-scale clinical trial examining the effects of eicosapentaenoic acid (EPA) on coronary artery disease (CAD) in hypercholesterolemic patients. Herein, we focused on risk factors other than low-density lipoprotein cholesterol (LDL-C) to investigate the effects of EPA on CAD among JELIS primary prevention cases.


METHODS
Hypercholesterolemic patients on statin therapy but without evidence of CAD (n=14,981) were randomly assigned to an EPA group (n=7503) or a control group (n=7478). The relationships between incident CAD, the number of CAD risk factors (hypercholesterolemia; obesity; high triglyceride (TG) or low high-density lipoprotein cholesterol (HDL-C); diabetes; and hypertension) and EPA treatment were investigated.


RESULTS
For the control and EPA groups combined, a higher number of risk factors was directly associated with an increased incidence of CAD. Incidence was lower for the EPA group than for the control group regardless of the numbers of risk factors. Compared to patients with normal serum TG and HDL-C levels, those with abnormal levels (TG >or=150 mg/dL; HDL-C <40 mg/dL) had significantly higher CAD hazard ratio (HR: 1.71; 95% CI: 1.11-2.64; P=0.014). In this higher risk group, EPA treatment suppressed the risk of CAD by 53% (HR: 0.47; 95% CI: 0.23-0.98; P=0.043).


CONCLUSIONS
Multiple risk factors besides cholesterol are associated with markedly increased incidence of CAD. High TG with low HDL-C represents a particularly potent risk factor. EPA was effective in reducing the incidence of CAD events for patients with this dyslipidemic pattern, suggesting that EPA may be especially beneficial in patients who with abnormal TG and HDL-C levels.
Saito
Yasushi
Y
Chiba University Graduate School of Medicine, Chiba, Japan. yasushi@faculty.chiba-u.jp
Yokoyama
Mitsuhiro
M
Origasa
Hideki
H
Matsuzaki
Masunori
M
Matsuzawa
Yuji
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; D008076:Cholesterol, HDL / Q000097:blood; D003324:Coronary Artery Disease / Q000517:prevention & control*; D019587:Dietary Supplements; D004359:Drug Therapy, Combination; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D015228:Hypertriglyceridemia / Q000150:complications / Q000188:drug therapy*; D007564:Japan; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy; D008875:Middle Aged; D017698:Postmenopause
D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015118:Eicosapentaenoic Acid