Omega-3 fatty acid supplementation and major cardiovascular events in maintenance haemodialysis: Systematic review and meta-analysis including PISCES

Background

Adults receiving maintenance haemodialysis (HD) face cardiovascular mortality rates approximately 20-fold higher than the general population, driven by a proinflammatory uraemic milieu, dyslipidaemia, and characteristically low circulating n-3 polyunsaturated fatty acid (PUFA) levels. The recently published event-driven PISCES trial provides the largest evidence base to date on n-3 PUFA supplementation in this population, warranting updated evidence synthesis.

Purpose

To evaluate the efficacy and safety of oral n-3 PUFA supplementation for reducing major cardiovascular events and cardiac death in adults receiving maintenance HD.

Methods

A systematic search to February 2026 identified double-blind RCTs of oral n-3 PUFA versus placebo in HD. The primary pooled outcome was time-to-first (TTF) major CV event or all-cause death, meta-analysed by inverse-variance methods under a random-effects model; a fixed-effect sensitivity analysis examined the 4 g/day subgroup. As PISCES's primary estimand was a recurrent-event model incompatible with TTF pooling, its TTF secondary HR was used for meta-analytic pooling.

Results

Three RCTs, encompassing 1,635 participants, met the inclusion criteria (OPACH, n=206; FISH, n=201; PISCES, n=1,228). In PISCES (4 g/day; median follow-up 3.5 years), n-3 PUFA significantly reduced the primary recurrent major cardiovascular event endpoint (HR 0.57; 95% CI 0.47–0.70; P<0.001), with an absolute risk reduction of 12.9% for TTF events (20.8% vs. 33.7%; NNT ≈8 over 3.5 years). For meta-analytic pooling, the PISCES TTF secondary analysis (HR 0.73; 95% CI 0.61–0.87) was used, as this is statistically commensurable with OPACH and FISH. The random-effects pooled TTF HR across all three trials was 0.77 (95% CI 0.55–1.09; I²=60%), not reaching statistical significance. In the high-dose subgroup (PISCES and FISH), the fixed-effect HR was 0.71 (95% CI 0.60–0.85). No excess serious bleeding was observed; in PISCES, bleeding events were numerically lower in the treatment arm (4.8% vs. 7.6%).

High-dose (4 g/day) oral n-3 PUFA supplementation significantly reduced major cardiovascular events in a single large event-driven trial, with consistent directional signals for cardiac death and myocardial infarction. Meta-analytic pooling across all trials did not reach statistical significance, with substantial between-trial heterogeneity limiting inference. Fixed-effect estimates in the high-dose subgroup are encouraging but require cautious interpretation given the small number of trials. The absence of excess serious bleeding is reassuring. Taken together, these findings support further evaluation of high-dose n-3 PUFA in HD but are insufficient to draw definitive conclusions about routine clinical implementation.Forest Plot 1Forest Plot 2