Association of anticoagulant-related bleeding events with cancer detection in atrial fibrillation: A systematic review and meta-analysis

Hellenic J Cardiol. 2021 Sep-Oct;62(5):359-365. doi: 10.1016/j.hjc.2020.11.007. Epub 2020 Nov 24.


Background: A bleeding episode may herald cancer in the general population. Oral anticoagulants (OACs), the mainstay treatment for atrial fibrillation (AF), are known to increase the risk of bleeding, and may thus promote an earlier diagnosis of cancer. Data regarding the association of bleeding episodes with cancer in patients with AF on OACs are scarce.

Methods: In this systematic review and meta-analysis, we searched electronic databases (Medline, Scopus, and Central) and gray literature sources for studies of patients with nonvalvular AF under any OAC, from inception until 14 October 2020. The primary outcome was the association of bleeding occurrences with the detection of cancer. A subgroup analysis was performed according to OAC type [NOAC (non-vitamin K oral anticoagulant) versus VKA (vitamin K antagonist)].

Results: Overall, 4 studies were included, accounting for a total of 144,362 patients with AF receiving OAC. During follow-up, 816 (0.57%) cases of cancer were confirmed. The presence of a bleeding event, either major or minor, was associated with a higher risk for cancer detection (odds ratio [OR] 8.79, 95% confidence interval [CI] 4.98-15.51, and I2 85%). Heterogeneity was explained after studies were stratified by the type of OAC (NOACs: OR 6.12, 95% CI 4.47-8.37, I2 0%, VKAs: OR 15.16, 95% CI 12.61-18.23, and I2 0%).

Conclusion: The detection of a bleeding event could be an alerting sign of cancer in patients with AF on OACs, particularly in patients receiving VKAs. REGISTRATION NUMBER (DOI): available in, DOI: 10.17605/OSF.IO/3948R.

Keywords: atrial fibrillation; bleeding; neoplasms; oral anticoagulants; warfarin.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Administration, Oral
  • Anticoagulants / adverse effects
  • Atrial Fibrillation* / complications
  • Atrial Fibrillation* / diagnosis
  • Atrial Fibrillation* / drug therapy
  • Hemorrhage / chemically induced
  • Hemorrhage / diagnosis
  • Hemorrhage / epidemiology
  • Humans
  • Neoplasms* / complications
  • Neoplasms* / drug therapy
  • Neoplasms* / epidemiology
  • Stroke*


  • Anticoagulants