The Optimal Dosage and Duration of ω-3 PUFA Supplementation in Heart Failure Management: Evidence from a Network Meta-Analysis

Abstract

ABSTRACT Heart failure is a progressive condition associated with a high mortality rate. Despite advancements in treatment, many patients continue to experience less-than-ideal outcomes. ω-3 (n–3) polyunsaturated fatty acids (PUFAs) have been studied as a potential supplementary therapy for heart failure, but the optimal dosage and duration of supplementation remain unclear. This network meta-analysis (NMA) aimed to assess the efficacy of various n–3 PUFA supplementation regimens in patients with heart failure, focusing on dose-dependent and timedependent effects. We conducted a systematic search for randomized controlled trials (RCTs) on n–3 PUFA supplementation in heart failure till 13 September, 2024. The primary outcome was the change in heart function, specifically left ventricular ejection fraction. Secondary outcomes included changes in peak oxygen consumption (VO2), blood B-type natriuretic peptide concentrations, and quality of life. The safety analysis focused on dropout rates (i.e., patients leaving the study for any reason before completion) and all-cause mortality. A frequentist-based NMA was performed. This NMA, which included 14 RCTs with 9075 participants (mean age, 66.0 y; 23.3% female), found that high-dose n–3 PUFA supplementation (2000–4000 mg/d) over a duration of 1 y significantly improved left ventricular ejection fraction and peak VO2 compared with those of control groups. Lower doses and shorter treatment periods did not produce the same benefits. No significant differences were found in dropout rates or all-cause mortality between the n–3 PUFAs and control groups. Long-term, highdose n–3 PUFA supplementation, particularly with a predominance of docosahexaenoic acid or eicosapentaenoic acid, enhances cardiac function in patients with heart failure without increasing risk of adverse events. Further well-designed RCTs with long treatment durations (i.e., >1 y) and stringent heart failure inclusion criteria are necessary to confirm these findings and reduce potential biases. This trial was registered at PROSPERO as CRD42024590476. Keywords: network meta-analysis, ω-3 polyunsaturated fatty acid, PUFA, EPA, DHA, heart failure, LVEF, cardiovascular disease