Fish-Oil Supplementation and Cardiovascular Events in Patients Receiving Hemodialysis

BACKGROUND: Cardiovascular disease is the leading cause of death in patients receiving hemodialysis, yet effective preventive therapies remain limited. Supplementation with n-3 polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may have cardiovascular benefits in the general population, but efficacy among patients receiving hemodialysis is uncertain. METHODS: In a double-blind, randomized, placebo-controlled trial conducted at 26 sites in Canada and Australia, we assigned adult patients receiving maintenance hemodialysis to daily supplementation with fish oil (4 g of n-3 polyunsaturated fatty acids [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: Between November 28, 2013, and July 22, 2019, a total of 1228 participants underwent randomization; 610 were assigned to the fish-oil group and 618 to the placebo group. During 3.5 years of follow-up, the rate of serious cardiovascular events was significantly lower in the fish-oil group than in the placebo group (0.31 vs. 0.61 per 1000 patient-days; hazard ratio, 0.57; 95% confidence interval [CI], 0.47 to 0.70; P<0.001). The rate of the extended primary end point that included noncardiac causes of death appeared to be lower in the fish-oil group than in the placebo group, with a hazard ratio of 0.77 (95% CI, 0.65 to 0.90). The hazard ratio for cardiac death was 0.55 (95% CI, 0.40 to 0.75); for fatal and nonfatal myocardial infarction, 0.56 (95% CI, 0.40 to 0.80); for peripheral vascular disease leading to amputation, 0.57 (95% CI, 0.38 to 0.86); for fatal and nonfatal stroke, 0.37 (95% CI, 0.18 to 0.76); and for a first cardiovascular event or death from any cause, 0.73 (95% CI, 0.61 to 0.87). Adherence to the trial regimen and the incidence of adverse events did not differ meaningfully between the groups. CONCLUSIONS: The rate of serious cardiovascular events among participants receiving maintenance hemodialysis was lower with daily supplementation with n-3 fatty acids than with placebo. (Supported by the Heart and Stroke Foundation of Canada and others; PISCES ClinicalTrials.gov number, ISRCTN00691795.).