Gastrointestinal Bleeding During Direct Oral Anticoagulants Therapy in Patients With Nonvalvular Atrial Fibrillation and Risk of Polypharmacy

Although concomitant medications have been raised as a factor affecting hemorrhage during direct oral anticoagulants (DOACs) therapy, details remain unelucidated. This study was conducted to clarify the relationship between concomitant medications with possible pharmacokinetic interactions and number of concomitant medications, and bleeding and embolism in patients with nonvalvular atrial fibrillation on DOACs. The subjects were 1,010 patients prescribed DOACs between April 2011 and June 2018. The study investigated their course between the first prescription and December 2018, including the presence or absence of clinically relevant bleeding, gastrointestinal bleeding (GIB), and major cardiovascular and cerebrovascular events (MACCE). Impacts of medications were evaluated by the general linear model with inverse probability-weighted propensity score. The observation period was 2,272 patient-years. The rate of bleeding was 4.7%/year, GIB was 2.8%/year, and MACCE was 2.0%/year. Taking 10 or more oral medications concurrently was a significant risk for GIB (hazard ratio, 2.046 [1.188–3.526]; p = 0.010). Nonsteroidal anti-inflammatory drugs (NSAIDs) was the only significant risk for GIB. Clinicians should be aware of gastrointestinal bleeding when using DOACs with patients taking more than 10 medications and/or NSAIDs.