The Optimal Dosage and Duration of Omega-3 Polyunsaturated Fatty Acid Supplementation in Heart Failure Management: Evidence from a Network Meta-Analysis.

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. Omega-3 polyunsaturated fatty acids (n-3 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 PUFAs supplementation regimens in heart failure patients, focusing on dose- and time-dependent effects. We conducted a systematic search for randomized controlled trials (RCTs) on n-3 PUFAs supplementation in heart failure up to September 13th, 2024. The primary outcome was the change in heart function, specifically left ventricular ejection fraction (LVEF). Secondary outcomes included changes in peak oxygen consumption (VO), blood BNP levels, 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 years, 23.3% female), found that high-dose n-3 PUFAs supplementation (2000-4000 mg/day) over a duration of at least one year significantly improved LVEF and peak VO compared to 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, high-dose n-3 PUFAs supplementation, particularly with a predominance of docosahexaenoic acid or eicosapentaenoic acid, enhances cardiac function in heart failure patients without increasing the risk of adverse events. Further well-designed RCTs with long treatment durations (i.e., more than one year) and stringent heart failure inclusion criteria are necessary to confirm these findings and reduce potential biases. TRIAL REGISTRATION: PROSPERO CRD42024590476.