Impact of Different Doses of Omega-3 Fatty Acids on Cardiovascular Outcomes: a Pairwise and Network Meta-analysis

Omega-3 fatty acid (O3FA) supplementation has shown conflicting evidence regarding its benefit in cardiovascular events. We performed a pairwise and network meta-analysis to elucidate the benefit of different doses of O3FA supplementation in cardiovascular prevention.

Fourteen studies were identified providing data on 125,763 patients. A prespecified cut-off value of < 1 g per day was set for low-dose (LD) O3FA and > 1 g per day for high-dose (HD) O3FA. The efficacy outcomes of interest were total death, cardiac death, sudden cardiac death, myocardial infarction, stroke, coronary revascularization, unstable angina, and major vascular events. Safety outcomes of interest were bleeding, gastrointestinal disturbances, and atrial fibrillation events. HD treatment was associated with a lower risk of cardiac death (IRR 0.79, 95% CI [0.65–0.96], p = 0.03 versus control), myocardial infarction (0.71 [0.62–0.82], p < 0.0001 versus control and 0.79 [0.67–0.92], p = 0.003 versus LD), coronary revascularization (0.74 [0.66–0.83], p < 0.0001 versus control and 0.74 [0.66–0.84], p < 0.0001 versus LD), unstable angina (0.73 [0.62–0.86], p = 0.0001 versus control and 0.74 [0.62–0.89], p = 0.002 versus LD), and major vascular events (0.78 [0.71–0.85], p < 0.0001 versus control and 0.79 [0.72–0.88], p < 0.0001 versus LD). HD treatment was associated with increased risk for bleeding events (1.49 [1.2–1.84], p = 0.0002 versus control and 1.63 [1.16–2.3], p = 0.005 versus LD) and increased atrial fibrillation events compared to control (1.35 [1.1–1.66], p = 0.004).

HD O3FA treatment was associated with lower cardiovascular events compared to LD and to control, but increased risk for bleeding and atrial fibrillation events.