ardiovascular 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.
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.
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.)
Results
Participants
The trial was conducted at 16 main sites and 10 satellite sites in Canada and Australia. The first participant underwent randomization on November 28, 2013, in the PISCES-Pilot and on August 27, 2015, in the current trial; the last participant underwent randomization on July 22, 2019. The date of the last participant follow-up was March 31, 2023. A total of 1228 participants underwent randomization and received at least one dose of fish oil or placebo (Fig. S1 in the Supplementary Appendix). Baseline characteristics were similar in the trial groups (Table 1 and Table S4). The mean (±SD) age of participants was 64.3±13.7 years, the mean duration of hemodialysis was 3.7±4.1 years, and 35.3% of the participants (434 of 1228) had a history of a cardiovascular event. The trial population appeared to be representative of patients receiving maintenance hemodialysis in the United States and participating countries. Over the course of the trial, there were 1394 patient-years of follow-up among 610 participants in the fish-oil group and 1382 patient-years of follow-up among 618 participants in the placebo group.
