Does concomitant treatment with NSAIDs increase the risk of bleeding in DOAC-treated patients?
Concomitant use of NSAIDs and DOACs increases bleeding risk, supporting guidelines that recommend acetaminophen, topical NSAIDs, or lower-risk NSAIDs like ibuprofen for pain management in these patients.
Direct oral anticoagulants (DOACs) are widely prescribed in patients at risk of thromboembolism. Although they are generally safer than warfarin, DOACs still carry a risk of bleeding and drug–drug interactions (DDIs). Nociceptive pain is common and may frequently occur in patients receiving DOAC therapy. In these cases, the European Society of Cardiology recommends avoiding non-steroidal anti-inflammatory drugs (NSAIDs) and preferring acetaminophen. However, acetaminophen is not effective when an inflammatory component is present. Consequently, non-pharmacological approaches or topical NSAIDs are suggested, while, in selected cases, lower-risk NSAIDs such as ibuprofen may be considered. Available evidence clearly indicates that concomitant treatment with NSAIDs and DOACs is associated with an increased risk of bleeding, although the magnitude of risk appears to differ across compounds. In this narrative review, we summarize the current evidence on bleeding risk associated with NSAID–DOAC coadministration, discuss potential DDIs from a pharmacokinetic perspective, and outline directions for future research.
Marcianò et al. (2026) studied this question.