Impact of NSAID Use on Bleeding Rates for Patients Taking Rivaroxaban or Apixaban.

Background: Posthoc analyses have found an increased bleeding risk in oral anticoagulation with concomitant nonsteroidal anti-inflammatory drug (NSAID) use. However, this research was primarily conducted in mixed populations prescribed both direct oral anticoagulants (DOACs) and warfarin. Research evaluating bleeding risk with NSAID use among DOACs alone is limited. This study evaluates bleeding rates in patients taking rivaroxaban and apixaban with and without NSAID use and investigates the potential impact of NSAID selectivity or proton pump inhibitor (PPI) coprescribing.

Methods: This single-center retrospective cohort study compared bleeding rates between rivaroxaban or apixaban among NSAID and non-NSAID users. The primary endpoint was a composite of any bleeding event per International Society on Thrombosis and Haemostatis criteria. The secondary endpoint was bleeding rates for NSAID users based on NSAID choice and PPI coprescribing.

Results: The study included 681 patients on rivaroxaban and 3225 patients on apixaban. Seventy-two patients on rivaroxaban (10.6%) and 300 patients on apixaban (9.3%) were NSAID users. There was no statistically significant difference between rivaroxaban and apixaban among NSAID users (hazard ratio 1.04; 95% CI, 0.98-1.12) or non-NSAID users (hazard ratio 1.15; 95% CI, 0.80-1.66). There was no clinically significant difference observed for NSAID selectivity or PPI coprescribing for NSAID users.

Conclusions: Bleeding rates were not significantly different between patients taking rivaroxaban and patients taking apixaban, regardless of NSAID use. A population health management tool may provide a safe approach for coprescribing NSAIDs with DOACs. Additional prospective studies are needed to quantify the comparative bleeding risk with concomitant NSAID use among DOACs alone.