Interpreting the PISCES trial on fish oil in hemodialysis patients: lessons on trial design, biological exposure, and outcome measurement

Patients receiving maintenance hemodialysis experience an exceptionally high cardiovascular risk, characterized by frequent recurrent events and a longstanding lack of effective preventive therapies. Most cardiovascular trials in this population have yielded neutral results, highlighting important limitations in both therapeutic strategies and outcome assessment. The PISCES trial recently reported significant reductions in both first and recurrent cardiovascular events with high-dose omega-3 fatty acids in patients undergoing hemodialysis, using a recurrent-event framework to capture overall cardiovascular burden. In this focused narrative review, we critically appraise the PISCES findings within the broader context of omega-3 research in chronic kidney disease and dialysis. Particular emphasis is placed on how biological exposure, population selection, and outcome frameworks influence the detectability of cardiovascular benefit in high-risk populations. PISCES challenges the prevailing notion that cardiovascular risk in hemodialysis is largely unmodifiable and underscores the importance of aligning therapeutic interventions with outcome measures that reflect total disease burden. More broadly, the trial illustrates how methodological choices may critically influence the interpretation of cardiovascular efficacy in populations with dense event clustering and high competing mortality.