Fish oil provides added benefits in statin users.(Clinical Rounds)

DALLAS -- Adding high-dose fish oil to a low-dose statin provided a 19% further reduction in major coronary events, compared with statins alone, Dr. Mitsuhiro Yokoyama reported at the annual scientific sessions of the American Heart Association.

The clinical benefits of fish oil apparently were achieved through lipid-independent mechanisms, since LDL cholesterol levels in the two study arms were reduced by an identical 26% in the 18,645-patient Japan Eicosapentaenoic Acid Lipid Intervention Study (JELIS).

JELIS involved nearly 15,000 Japanese patients being treated for primary prevention of coronary heart disease and more than 3,600 others undergoing secondary prevention. All were placed on either 5 mg/day of simvastatin or 10 mg/day of pravastatin and then randomized to 1,800 mg/day of eicosapentaenoic acid (EPA) from high-dose fish oil capsules or not. The study was open label but featured blinded adjudication of outcomes, explained Dr. Yokoyama, professor and chief of the division of cardiovascular and respiratory medicine at Kobe University.

After a mean of 4.6 years of follow-up, the primary combined study end point--a composite of sudden cardiac death, MI, unstable angina, and/or coronary revascularization--occurred in 2.8% of patients on statin plus fish oil, compared with 3.5% of controls, a highly significant difference.

In the secondary prevention cohort the event rate was 10.7% in controls and 8.7% with dual therapy, a 19% risk reduction. A nearly identical 18% relative risk reduction was seen with dual therapy in the primary prevention cohort; however, this benefit did not achieve statistical significance because event rates were only about one-sixth those in the secondary prevention group.

The high-dose fish oil was well tolerated. The chief side effect--mild GI upset--occurred in 3.8% of recipients, a rate more than twice that in controls. Skin rash and/or itching occurred in 1.7% of the fish oil group and 0.7% of controls. On the other hand, complaints of joint or muscle pain ...