CardioExchange Archive

Another large study has failed to find any benefits for fish oil supplements. The Italian Risk and Prevention Study, published in the New England Journal of Medicine, enrolled 12,513 people who had not had a myocardial infarction but had evidence of atherosclerosis or had multiple cardiovascular risk factors. The patients were randomized to either a fish oil supplement (1 g daily of omega-3 fatty acids) or placebo.

After 5 years’ follow-up, the primary endpoint — the time to death from cardiovascular causes or admission to the hospital for cardiovascular causes — had occurred in 11.7% of the fish oil group versus 11.9% of the placebo group (adjusted hazard ratio 0.97, CI 0.88-1.08, p=0.58). There were no significant differences in any of the prespecified secondary endpoints.

With one exception, there were no significant differences in outcomes in the prespecfied subgroups. Women who received fish oil supplements had a significant reduction in the primary endpoint (HR 0.82, CI 0.67-0.99, p=0.04). The study investigators also report that although there was no difference in the rate of hospital admissions for cardiovascular causes, there was a significant reduction in hospital admissions for heart failure in the fish oil group (1.5% vs. 2.3%, p=0.002).

Due to a lower-than-expected rate of events, after the first year the investigators modified the primary endpoint, which originally had been the cumulative rate of death, MI, and nonfatal stroke.

The investigators write that “the consistently null effect across the various end points and subgroups does not suggest alternative interpretations.” The observed benefits in women and in reducing hospital admissions for heart failure “must be considered conservatively,” they add.

The trial investigators discussed two previous Italian trials, the GISSI-Prevenzione trial, in MI patients, and the GISSI-HF trial, in heart failure patients, which found benefits for fish oil supplements in their respective populations. In both trials, they say, the benefit may be attributed to a reduction in sudden deaths from cardiac causes. “It is conceivable that the effects of n-3 fatty acids become manifest primarily in patients who are particularly prone to ventricular arrhythmic events,” they write. The population in the current trial, by contrast, was much less prone to arrhythmias.

One expert on cardiovascular prevention, James Stein, said that “the results are disappointing, but consistent with recent studies showing no significant effect of fish oil supplements.” He said that fish oil supplements “are not a panacea” and that it would be most accurate to say that “some studies suggest a benefit.”

Dariush Mozaffarian, a leading researcher in the field, sent the following comment:

Heart disease death (rather than nonfatal heart disease or total cardiovascular disease) is the main outcome likely influenced by fish oil, at least at relatively low doses such as used in this trial. Thus, this is an important study, because among the more recent trials of fish oil and heart disease, it is the only one that has larger numbers of heart disease deaths (158 total).

The lack of any discernable effect on heart disease death (“coronary death”) raises concerns about the real benefits of fish oil supplements in patients at high risk for cardiovascular disease. Recommendations to eat fish, in the context of an overall healthy diet, increasing activity, and stopping smoking, should remain the priority for reducing risk. Still, there was no evidence that fish oil supplements cause any harm or risk, so for patients who won’t eat fish or wish to be sure they are getting their omega-3’s, there is no reason to stop taking fish oil supplements if they are already on them.