Omega-3 Polyunsaturated Fatty Acids Supplements and Cardiovascular Disease Outcome: A Systematic Review and Meta-Analysis on Randomized Controlled Trials

Background: Many meta-analyses and randomized controlled trials (RCTs) on the use of Omega-3 supplements for cardiovascular dis-ease (CVD) have come to different outcomes. Besides, previous meta-analyses have missed some key RCTs on this topic. Methods: PubMed, EMBASE, Cochrane Library and Web of Science were manually searched for eligible RCTs on Omega-3 polyunsaturated fatty acids (PUFA) use for CVD. Risk estimates of each relevant outcome were calculated as a hazard ratio (HR) with 95% confidence interval (95% CI) using the random-effects model. Subgroup analysis was conducted according to the main characteristics of the population, sensitivity analysis would be performed if there was significant heterogeneity among analyses on relevant outcomes. Statistical het-erogeneity was assessed using chi-square tests and quantified using I-square statistics. Results: Nineteen eligible RCTs incorporating 116,498 populations were included. Omega-3 PUFA supplementation could not significantly improve the outcomes of major adverse cardiovascular events (MACE) (HR: 0.98, 95% CI: 0.91-1.06), myocardial infarction (MI) (HR: 0.86, 95% CI: 0.70-1.05), coronary heart disease (CHD) (HR: 0.90, 95% CI: 0.80-1.01), stroke (HR: 1.00, 95% CI: 0.91-1.10), SCD (sudden cardiac death) (HR: 0.90, 95% CI: 0.80-1.02), all-cause mortality (HR: 0.96, 95% CI: 0.89-1.04), hospitalization (HR: 0.99, 95% CI: 0.81-1.20), hospitalization for all heart disease (HR: 0.91, 95% CI: 0.83-1.00), hospitalization for heart failure (HR: 0.97, 95% CI: 0.91-1.04). Although omega-3 PUFA significantly reduced revascularization (HR: 0.90, 95% CI: 0.81-1.00) and cardiovascular mortality (CV mortality) (HR: 0.91, 95% CI: 0.85-0.97), risk for atrial fibrillation (AF) was also increased (HR: 1.56, 95% CI: 1.27-1.91). Subgroup analysis results kept consistent with the main results. Conclusions: Omega-3 PUFA supplementation could reduce the risk for CV mortality and revascularization, it also increased the AF incidence. No obvious benefits on other CVD outcomes were identified. Overall, potential CVD benefits and harm for AF should be balanced when using omega-3 PUFA for patients or populations at high risk.