Dose-related meta-analysis for Omega-3 fatty acids supplementation on major adverse cardiovascular events

Background & aims: Omega-3 supplements are widely used for cardiovascular (CV) protection. We performed an updated meta-analysis for omega-3 and CV outcomes. Methods: Random-effects meta-analysis including double-blind RCTs with duration >= 1 year, evaluating omega-3 supplements in 4 a priori defined categories (<1, 1, 2, >= 3 of 1g capsules/day) on all-cause mortality, cardiac death, myocardial infarction and stroke, reporting the relative risk (RR) as the measure of interest. Complementary approaches were Trial Sequential Analysis (TSA) and sensitivity analyses for triglycerides, prevention setting, intention-to-treat analysis, eicosapentaenoic acid (EPA), sample size, statin use and study duration. Results: Nineteen randomized controlled trials (RCTs) with 97,709 participants were included. Omega-3 supplements were not statistically significantly associated with reduced all-cause mortality, cardiac death, MI, or stroke, with the exception of reduced cardiac mortality only for the equivalent dose of 2 capsules/day (RR 0.55, 95%CI 0.33, 0.90, p = 0.0169, I-2 = 0%). TSA reached the required information size only for the lower doses regarding all-cause and cardiac mortality, where they show no significant association. Meta-regression on EPA dose, as well as the majority of sensitivity analyses did not show any statistically significant association. Conclusion: Compared to the robust evidence for low doses, higher doses and particularly for the unique type of omega-3 icosapent ethyl ester should be further addressed. (C) 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.