Fish oils have no effect on cardiovascular morbidity and mortality in patients with multiple risk factors or atherosclerotic vascular disease, a large general practice-based study from Italy has found.

The Risk and Prevention Study was double-blind and placebo-controlled. A total of 12,513 patients were enrolled who had multiple cardiovascular risk factors or atherosclerotic vascular disease but none had had a myocardial infarction (MI). They were followed up by a network of 860 GPs.

Around half, 6,244 patients, were assigned to 1 g/day of n-3 fatty acids (polyunsaturated fatty acid ethyl esters with eicosapentaenoic acid and docosahexaenoic acid content not less than 85%) and 6,269 to placebo.

The primary end point was initially a composite that included death, nonfatal MI and nonfatal stroke but was later revised at one year after a blinded assessment showed a very low event rate. The revised primary end point was death from cardiovascular causes or hospital admissions for cardiovascular problems. The median follow-up was five years.

There were no significant differences in death from cardiovascular causes or hospitalisations for CVD between the two groups: 11.7% in the fish oil group and 11.9% in the placebo group, adjusted hazard ratio (HR) with n−3 fatty acids, 0.97 (95% CI:0.88-1.08; P = 0.580. Furthermore, none of the secondary end points showed a significant effect of fish oils either: death, non-fatal MI or stroke (P = 0.64), death from cardiovascular cause or nonfatal MI or stroke (P = 0.59), fatal or nonfatal coronary event (P = 0.51) and death from coronary cause (P = 0.66).

Fish oils or more specifically n−3 polyunsaturated fatty acids are considered to be of benefit in patients with a previous MI or heart failure.

This is based on the findings of the GISSI and GISSI-HF trials.

Patients and physicians may be tempted to extrapolate this data to consider that taking fish oil supplements may be of benefit in those with multiple cardiovascular risk factors or atherosclerotic vascular disease without prior MI. The Risk and Prevention Study has shown this not to be the case.

The dose of fish oil used was the same as in previous studies such as GISSI and GISSI-HF which did show a benefit in the reduction of sudden cardiac death postulated to be via suppression of ventricular arrhythmias. Other recent trials such as the Alpha Omega trial and the OMEGA trial have questioned the role of fish oils post-MI.

The fish oil supplements were well tolerated and did not appear to cause harm but the evidence base to support their use in patients at high risk of CVD is lacking and it is possible that this may soon extend to their use post-MI.

Dr Peter Savill