Background and aims: The bleeding risk of using non-steroidal anti-inflammatory drugs (NSAIDs) in patients treated with oral anticoagulants for venous thromboembolism (VTE) remains unclear.
Methods: A nationwide cohort study of 51 794 VTE patients initiating oral anticoagulants between 1 January 2012 and 31 December 2022 was conducted. Time-dependent multivariate cause-specific Cox regression was used to compute adjusted hazard ratios between NSAID use and hospital-diagnosed bleeding episodes.
Results: Event rates for any bleeding per 100 person-years were 3.5 [95% confidence interval (CI), 3.4-3.7] during periods without NSAID use and 6.3 (95% CI, 5.1-7.9) during periods with NSAID use (number needed to harm = 36 patients treated for 1 year). Compared with non-use, the adjusted hazard ratios for any bleeding associated with NSAID use were 2.09 (95% CI, 1.67-2.62) overall, 1.79 (95% CI, 1.36-2.36) for ibuprofen, 3.30 (95% CI, 1.82-5.97) for diclofenac, and 4.10 (95% CI, 2.13-7.91) for naproxen. Compared with non-use, the adjusted hazard ratios associated with NSAID use were 2.24 (95% CI, 1.61-3.11) for gastrointestinal bleeding, 3.22 (95% CI, 1.69-6.14) for intracranial bleeding, 1.36 (95% CI, .67-2.77) for thoracic and respiratory tract bleeding, 1.57 (95% CI, .98-2.51) for urinary tract bleeding, and 2.99 (95% CI, 1.45-6.18) for anaemia caused by bleeding. Results were consistent for anticoagulant and VTE subtypes.
Conclusions: Patients treated with oral anticoagulants for VTE had a more than two-fold increased bleeding rate when using NSAIDs. This increased bleeding rate was not restricted to the gastrointestinal tract.
Keywords: Anti-inflammatory agents; Anticoagulants; Epidemiology; Haemorrhage; Non-steroidal; Venous thromboembolism.
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.