Risk of bleeding with concomitant use of oral anticoagulants and aspirin: A systematic review and meta-analysis

Abstract

Purpose: Oral anticoagulants (OACs) and aspirin can trigger bleeding events when used alone or in combination. The purpose of this study was to compare the risk of any type of bleeding in individuals exposed to a combination of OAC and aspirin with the risk in those taking an OAC or aspirin alone.

Methods: MEDLINE and Web of Science were queried in January 2021 for eligible articles. Studies were included if they were either randomized controlled trials (RCTs) or observational studies and evaluated the number of any bleeding events in two groups, one with exposure to both OAC and aspirin and one with exposure to OAC alone or aspirin alone. Pooled odds ratios were calculated using a random-effects model.

Results: Forty-two studies were included. In an analysis of 15 RCTs and 19 observational studies evaluating OAC plus aspirin versus OAC alone, a significant difference in the risk of bleeding was observed in the combination groups, with an odds ratio [OR] of, 1.36 (95% CI, 1.15-1.59) for RCTs and an OR of 1.42 (95% CI-, 1.09-1.87) for observational studies. When OAC plus aspirin was compared to aspirin alone, a higher rate of bleeding was found in the combination group (OR, 2.36; 95%CI, 1.91-2.92) in the analysis of 15 RCTs, but no significant difference was found among 10 observational studies (OR, 1.93; 95% Cl, 0.99-3.75).

Conclusion: The risk of any type of bleeding was significantly increased among patients taking aspirin plus OAC compared to those taking OAC alone in both RCTs and observational studies. Evaluation of RCTs comparing OAC plus aspirin to aspirin alone suggests increased bleeding risk as well.

Keywords: anticoagulants; bleeding risk; drug interaction; gastrointestinal bleeding; salicylates; warfarin.