Evidence map›Paper›PMID 34612056›Full record

SynthesisCirculation2021

Effect 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.

Baris Gencer, Luc Djousse, Omar T Al-Ramady, Nancy R Cook, JoAnn E Manson, Christine M Albert

Registry-linked trialOpen access · hybridAbstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Circulation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02178410 (Vitamin D and Omega-3 Trial), which is not on this map. Cited by 82 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 11 pooled it
11.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02178410 phase3active not recruitingnot on this map

Vitamin D and Omega-3 Trial (VITAL Rhythm Study)

TypeinterventionalSponsorBrigham and Women's HospitalRan2012 to 2026Enrolled25,119ConditionsCardiovascular DiseaseArmsVitamin D3, Omega-3 fatty acids (fish oil), Fish oil placebo, Vitamin D3 placebo
3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 11 syntheses or guidelines pooled it, 133 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Guideline
  6. Guideline
  7. Pooled it
  8. Pooled it
  9. Pooled it
  10. Pooled it
  11. Pooled it
  12. Trial
  13. Trial
  14. Trial
  15. Review
  16. Polyunsaturated Fatty Acids and Atrial Fibrillation: Friend or Foe?Journal of atherosclerosis and thrombosis · 2026
    Article
  17. Article
  18. Review
  19. Review
  20. Article

22 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Baris GencerCardiology Division, Geneva University Hospitals, Switzerland (B.G.).ORCID 0000-0002-8954-9694
Luc DjousseDepartment of Medicine, Brigham and Women's Hospital, Boston, MA (L.D., O.T.A., N.R.C., J.E.M.).
Omar T Al-RamadyDepartment of Medicine, Brigham and Women's Hospital, Boston, MA (L.D., O.T.A., N.R.C., J.E.M.).
Nancy R CookDepartment of Medicine, Brigham and Women's Hospital, Boston, MA (L.D., O.T.A., N.R.C., J.E.M.).
JoAnn E MansonDepartment of Medicine, Brigham and Women's Hospital, Boston, MA (L.D., O.T.A., N.R.C., J.E.M.).
Christine M AlbertDepartment of Cardiology, Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA (C.M.A.).ORCID 0000-0002-2081-1121
Brigham and Women's Hospital · USBern University of Applied Sciences · CHCedars-Sinai Smidt Heart Institute · US

Funding

VITamin D and omegA-3 triaL (VITAL)U01CA138962 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E., MANSON, JOANN ELISABETH · 2009 to 2014
$23.6M
The VITamin D and OmegA-3 TriaL (VITAL)R01CA138962 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E., MANSON, JOANN ELISABETH · 2015 to 2019
$20.9M
The VITamin D and OmegA-3 TriaL (VITAL): Post-Intervention Follow-UpR01AT011729 · NCCIH · BRIGHAM AND WOMEN'S HOSPITAL · PI Jun Li, JoAnn Elisabeth Manson · 2021 to 2026
$5.2M
The VITAL Rhythm StudyR01HL116690 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI ALBERT, CHRISTINE M · 2013 to 2020
$3.5M
NCCIH NIH HHS R01 AT011729NCI NIH HHS R01 CA138962NCI NIH HHS U01 CA138962NHLBI NIH HHS R01 HL116690
6 · The paper itself

Abstract

backgroundSome, 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.

methodsThe 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.

resultsOf 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];

conclusionsIn 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.

Indexed as

AgedAnimalsAtrial FibrillationCardiovascular DiseasesDietary SupplementsFatty Acids, Omega-3FemaleFishesHumansMaleRisk FactorsTreatment OutcomeFatty Acids, Omega-3atrial fibrillationclinical trialsdietary supplementsfatty acids, omega-3meta-analysis

Identifiers

PMID34612056
PMCPMC9109217
OpenAlexW3203031064

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.