biostudies-literatureGencer BNCCIH NIH HHSNHLBI NIH HHSNCI NIH HHS1981-1990https://www.ebi.ac.uk/biostudies/studies/S-EPMC9109217biostudies-literatureUnknown144(25)<h4>Background</h4>Some, but not all, large-scale randomized controlled trials (RCTs) investigating the effects of marine ɷ-3 fatty acids supplementation on cardiovascular outcomes have reported increased risks of atrial fibrillation (AF). The potential reasons for disparate findings may be dose-related.<h4>Methods</h4>The MEDLINE and Embase databases were searched for articles and abstracts published between January 1, 2012, and December 31, 2020, in addition to a meta-analysis of large cardiovascular RCTs published in 2019. RCTs of cardiovascular outcomes of marine ɷ-3 fatty acids that reported results for AF, either as a prespecified outcome, an adverse event, or a cause for hospitalization, with a minimum sample size of 500 patients and a median follow-up of at least 1 year were included. RCTs specifically examining shorter-term effects of ɷ-3 fatty acids on recurrent AF in patients with established AF or postoperative AF were not included. The hazard ratio (HR) for the reported AF outcomes within each trial was meta-analyzed using random effects model with Knapp-Hartung adjustment and evaluated a dose-response relationship with a meta-regression model.<h4>Results</h4>Of 4049 screened records, 7 studies were included in the meta-analysis. Of those, 5 were already detected in a previous meta-analysis of cardiovascular RCTs. Among the 81 210 patients from 7 trials, 58 939 (72.6%) were enrolled in trials testing ≤1 g/d and 22 271 (27.4%) in trials testing >1 g/d of ɷ-3 fatty acids. The mean age was 65 years, and 31 842 (39%) were female. The weighted average follow-up was 4.9 years. In meta-analysis, the use of marine ɷ-3 fatty acid supplements was associated with an increased risk of AF (n=2905; HR, 1.25 [95% CI, 1.07-1.46]; <i>P</i>=0.013). In analyses stratified by dose, the HR was greater in the trials testing >1 g/d (HR, 1.49 [95% CI, 1.04-2.15]; <i>P</i>=0.042) compared with those testing ≤1 g/d (HR, 1.12 [95% CI, 1.03-1.22]; <i>P</i>=0.024; <i>P</i> for interaction <0.001). In meta-regression, the HR for AF increased per 1 g higher dosage of ɷ-3 fatty acids dosage (HR, 1.11 [95% CI, 1.06-1.15]; <i>P</i>=0.001).<h4>Conclusions</h4>In RCTs examining cardiovascular outcomes, marine ɷ-3 supplementation was associated with an increased risk of AF. The risk appeared to be greater in trials testing >1 g/d.CirculationEffect of Long-Term Marine ɷ-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.PMC9109217R01 AT011729U01 CA138962R01 HL116690R01 CA138962Gencer BManson JECook NRAl-Ramady OTDjousse LAlbert CMfalseEffect of Long-Term Marine ɷ-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.<h4>Background</h4>Some, but not all, large-scale randomized controlled trials (RCTs) investigating the effects of marine ɷ-3 fatty acids supplementation on cardiovascular outcomes have reported increased risks of atrial fibrillation (AF). The potential reasons for disparate findings may be dose-related.<h4>Methods</h4>The MEDLINE and Embase databases were searched for articles and abstracts published between January 1, 2012, and December 31, 2020, in addition to a meta-analysis of large cardiovascular RCTs published in 2019. RCTs of cardiovascular outcomes of marine ɷ-3 fatty acids that reported results for AF, either as a prespecified outcome, an adverse event, or a cause for hospitalization, with a minimum sample size of 500 patients and a median follow-up of at least 1 year were included. RCTs specifically examining shorter-term effects of ɷ-3 fatty acids on recurrent AF in patients with established AF or postoperative AF were not included. The hazard ratio (HR) for the reported AF outcomes within each trial was meta-analyzed using random effects model with Knapp-Hartung adjustment and evaluated a dose-response relationship with a meta-regression model.<h4>Results</h4>Of 4049 screened records, 7 studies were included in the meta-analysis. Of those, 5 were already detected in a previous meta-analysis of cardiovascular RCTs. Among the 81 210 patients from 7 trials, 58 939 (72.6%) were enrolled in trials testing ≤1 g/d and 22 271 (27.4%) in trials testing >1 g/d of ɷ-3 fatty acids. The mean age was 65 years, and 31 842 (39%) were female. The weighted average follow-up was 4.9 years. In meta-analysis, the use of marine ɷ-3 fatty acid supplements was associated with an increased risk of AF (n=2905; HR, 1.25 [95% CI, 1.07-1.46]; <i>P</i>=0.013). In analyses stratified by dose, the HR was greater in the trials testing >1 g/d (HR, 1.49 [95% CI, 1.04-2.15]; <i>P</i>=0.042) compared with those testing ≤1 g/d (HR, 1.12 [95% CI, 1.03-1.22]; <i>P</i>=0.024; <i>P</i> for interaction <0.001). In meta-regression, the HR for AF increased per 1 g higher dosage of ɷ-3 fatty acids dosage (HR, 1.11 [95% CI, 1.06-1.15]; <i>P</i>=0.001).<h4>Conclusions</h4>In RCTs examining cardiovascular outcomes, marine ɷ-3 supplementation was associated with an increased risk of AF. The risk appeared to be greater in trials testing >1 g/d.2021-01-01T00:00:00Z2021 Dec2026-06-05T06:00:38.808Z2026-05-13T14:29:06.845ZS-EPMC91092173461205610.1161/circulationaha.121.05565410.1161/CIRCULATIONAHA.121.055654