Fish oil may lower rate of serious cardiovascular events for those undergoing hemodialysis, study finds

The rate of serious cardiovascular events among patients on maintenance hemodialysis was lower with daily supplementation with n-3 fatty acids than with placebo, a study found.

To study the effects of supplementation with n-3 polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), researchers conducted a double-blind, randomized trial at 16 main sites and 10 satellite sites in Canada and Australia. Patients receiving maintenance hemodialysis were assigned to daily supplementation with fish oil (4 g of n-3 polyunsaturated fatty acids, including 1.6 g of EPA and 0.8 g of DHA) or corn-oil placebo.

The primary end point was a composite of all serious cardiovascular events, including sudden and nonsudden cardiac death, fatal and nonfatal myocardial infarction, peripheral vascular disease leading to amputation, and fatal and nonfatal stroke. Secondary end points included extension of the primary end point to include noncardiac causes of death, the individual components of the primary end point, and a first cardiovascular event or death from any cause. Results were published on Nov. 7 by the New England Journal of Medicine.

Between November 2013 and July 2019, there were 1,394 patient-years of follow-up for 610 participants in the fish-oil group and 1,382 patient-years of follow-up for 618 participants in the placebo group. The rate of serious cardiovascular events was significantly lower in the fish-oil group compared to placebo (0.31 vs. 0.61 per 1,000 patient-days; hazard ratio [HR], 0.57 [95% CI, 0.47 to 0.70]; P<0.001), as was the rate of the extended primary end point (HR, 0.77; 95% CI, 0.65 to 0.90). The hazard ratio was 0.55 (95% CI, 0.40 to 0.75) for cardiac death, 0.56 (95% CI, 0.40 to 0.80) for fatal and nonfatal myocardial infarction, 0.57 (95% CI, 0.38 to 0.86) for peripheral vascular disease leading to amputation, 0.37 (95% CI, 0.18 to 0.76) for fatal and nonfatal stroke, and 0.73 (95% CI, 0.61 to 0.87) for a first cardiovascular event or death from any cause.

Adherence to the trial regimen and incidence of adverse events did not differ meaningfully between the groups. There was serious bleeding in 4.8% of the fish-oil group and 7.6% of the placebo group.

The study authors speculated that n-3 fatty acids might lower the stimuli for arrhythmias. Because patients treated with hemodialysis have low levels of n-3 fatty acid, the cardioprotective properties of n-3 fatty acids may be especially beneficial, they stated.

An accompanying editorial called the results impressive and said that the lack of therapies available for patients receiving maintenance hemodialysis may lead clinicians to strongly consider n-3 polyunsaturated fatty acids, even in the absence of a significant difference in all-cause mortality. “On the other hand, contemporary medicine is replete with examples in which potentially practice-changing, outsized results of early trials have failed to be replicated,” the editorialists wrote. “This situation suggests that we should pause before accepting such remarkable results as gospel.”