JAMA Intern Med. 2014 Jun;174(6):947-53. doi: 10.1001/jamainternmed.2014.946.
Davidson BL1, Verheijen S2, Lensing AW3, Gebel M4, Brighton TA5, Lyons RM6, Rehm J7, Prins MH8.
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.