Omega‐3 fatty acids for the primary and secondary prevention of cardiovascular disease

Background Omega‐3 polyunsaturated fatty acids from oily fish (long‐chain omega‐3 (LCn3)), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), as well as from plants (alpha‐linolenic acid (ALA)) may benefit cardiovascular health. Guidelines recommend increasing omega‐3‐rich foods, and sometimes supplementation, but recent trials have not confirmed this. Objectives To assess the effects of increased intake of fish‐ and plant‐based omega‐3 fats for all‐cause mortality, cardiovascular events, adiposity and lipids. Search methods We searched CENTRAL, MEDLINE and Embase to February 2019, plus ClinicalTrials.gov and World Health Organization International Clinical Trials Registry to August 2019, with no language restrictions. We handsearched systematic review references and bibliographies and contacted trial authors. Selection criteria We included randomised controlled trials (RCTs) that lasted at least 12 months and compared supplementation or advice to increase LCn3 or ALA intake, or both, versus usual or lower intake. Data collection and analysis Two review authors independently assessed trials for inclusion, extracted data and assessed validity. We performed separate random‐effects meta‐analysis for ALA and LCn3 interventions, and assessed dose‐response relationships through meta‐regression. Main results We included 86 RCTs (162,796 participants) in this review update and found that 28 were at low summary risk of bias. Trials were of 12 to 88 months' duration and included adults at varying cardiovascular risk, mainly in high‐income countries. Most trials assessed LCn3 supplementation with capsules, but some used LCn3‐ or ALA‐rich or enriched foods or dietary advice compared to placebo or usual diet. LCn3 doses ranged from 0.5 g a day to more than 5 g a day (19 RCTs gave at least 3 g LCn3 daily). Meta‐analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all‐cause mortality (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.93 to 1.01; 143,693 participants; 11,297 deaths in 45 RCTs; high‐certainty evidence), cardiovascular mortality (RR 0.92, 95% CI 0.86 to 0.99; 117,837 participants; 5658 deaths in 29 RCTs; moderate‐certainty evidence), cardiovascular events (RR 0.96, 95% CI 0.92 to 1.01; 140,482 participants; 17,619 people experienced events in 43 RCTs; high‐certainty evidence), stroke (RR 1.02, 95% CI 0.94 to 1.12; 138,888 participants; 2850 strokes in 31 RCTs; moderate‐certainty evidence) or arrhythmia