- This study estimated the bleeding risk when the use of anticoagulant therapy (rivaroxaban or enoxaparin–vitamin K antagonist) was combined with either an NSAID or aspirin therapy in patients with VTE enrolled in clinical trials from 2007 to 2009. Clinically relevant bleeding was higher with combined use compared with anticoagulant use alone (HR, 1.77; 95% CI, 1.46–2.14). Major bleeding was also increased with combined use.
- Risk of clinically relevant and major bleeding should be considered when anticoagulant therapy is used concomitantly with an NSAID or aspirin.
ABSTRACT
IMPORTANCE
Combined anticoagulant and aspirin therapy is associated with increased bleeding risk in patients with atrial fibrillation, but the bleeding risk of combined use of anticoagulant and nonsteroidal anti-inflammatory drugs (NSAIDs) is poorly documented.
OBJECTIVE
To estimate the bleeding risk of combined anticoagulant (rivaroxaban or enoxaparin–vitamin K antagonist [VKA]) and NSAID or aspirin therapy in patients with venous thromboembolism.
DESIGN, SETTING, AND PARTICIPANTS
Prospective analysis of observational data from the EINSTEIN deep vein thrombosis and pulmonary embolism clinical trials comparing rivaroxaban with enoxaparin-VKA treatment, trials performed in hospitals and clinics in 8246 patients enrolled from 2007 to 2009.
EXPOSURE
Bleeding event rates during exposure to NSAID and aspirin therapy were compared to time without exposure.
MAIN OUTCOMES AND MEASURES
Days of NSAID or aspirin use and nonuse, clinically relevant bleeding event and major bleeding event rates by patient-years, and hazard ratios.
RESULTS
During NSAID-anticoagulant concomitant treatment, clinically relevant bleeding occurred with an event rate of 37.5 per 100 patient-years vs 16.6 per 100 patient-years during anticoagulant use only (hazard ratio [HR], 1.77 [95% CI, 1.46-2.14]). Major bleeding during NSAID-anticoagulant treatment occurred with an event rate of 6.5 per 100 patient-years, compared to 2.0 per 100 patient-years during nonuse (HR, 2.37 [95% CI, 1.51-3.75]). For aspirin-anticoagulant concomitant treatment, clinically relevant bleeding occurred with an event rate of 36.6 per 100 patient-years, compared to 16.9 per 100 patient-years during aspirin nonuse (HR, 1.70 [95% CI, 1.38-2.11]). Major bleeding in aspirin-anticoagulant–treated patients occurred with an event rate of 4.8 per 100 patient-years, compared to 2.2 per 100 patient-years during aspirin nonuse (HR, 1.50 [95% CI, 0.86-2.62]). Increases in risk for clinically relevant and major bleeding were similar for rivaroxaban and enoxaparin-VKA anticoagulation regimens.
CONCLUSIONS AND RELEVANCE
Among patients with venous thromboembolism receiving anticoagulant therapy, concomitant use of an NSAID or aspirin is associated with an increased risk of clinically relevant and major bleeding.
JAMA internal medicine
Bleeding Risk of Patients With Acute Venous Thromboembolism Taking Nonsteroidal Anti-Inflammatory Drugs or Aspirin
JAMA Intern Med 2014 Apr 14;[EPub Ahead of Print], BL Davidson, S Verheijen, AWA Lensing, M Gebel, TA Brighton, RM Lyons, J Rehm, MH Prins