Chang SH, et al. - The objectives of this study were to evaluate the relationship between utilization of non–vitamin K oral anticoagulants (NOACs) with and without concurrent medications and risk of major bleeding in patients with nonvalvular atrial fibrillation. Among patients taking NOACs for nonvalvular atrial fibrillation, concurrent utilization of amiodarone, fluconazole, rifampin, and phenytoin compared with the utilization of NOACs alone, was related to increased risk of major bleeding. Physicians prescribing NOAC medications ought to consider the potential risks related to concomitant utilization of other drugs.

Methods

• For this research, they designed a retrospective cohort study.
• This study used data from the Taiwan National Health Insurance database and included 91330 patients with nonvalvular atrial fibrillation who received not less than1 NOAC prescription of dabigatran, rivaroxaban, or apixaban from January 1, 2012, through December 31, 2016, with final follow-up on December 31, 2016.

Results

• Out of 91330 patients with nonvalvular atrial fibrillation (mean age, 74.7 years [SD, 10.8]; men, 55.8%; NOAC exposure: dabigatran, 45347 patients; rivaroxaban, 54006 patients; and apixaban, 12886 patients), 4770 major bleeding events occurred during 447037 person-quarters with NOAC prescriptions.
• The most widely recognized medications co-prescribed with NOACs over all person-quarters were atorvastatin (27.6%), diltiazem (22.7%), digoxin (22.5%), and amiodarone (21.1%).
• Concurrent utilization of amiodarone, fluconazole, rifampin, and phenytoin with NOACs had a significant increase in adjusted incidence rates per 1000 person-years of major bleeding than NOACs alone: 38.09 for NOAC use alone vs 52.04 for amiodarone (difference, 13.94 [99% CI, 9.76-18.13]); 102.77 for NOAC use alone vs 241.92 for fluconazole (difference, 138.46 [99% CI, 80.96-195.97]); 65.66 for NOAC use alone vs 103.14 for rifampin (difference, 36.90 [99% CI, 1.59-72.22); and 56.07 for NOAC use alone vs 108.52 for phenytoin (difference, 52.31 [99% CI, 32.18-72.44]; P < .01 for all comparisons).
• Compared with NOAC use alone, the adjusted incidence rate for major bleeding was significantly lower for concurrent utilization of atorvastatin, digoxin, and erythromycin or clarithromycin and was not significantly different for concurrent utilization of verapamil; diltiazem; cyclosporine; ketoconazole, itraconazole, voriconazole, or posaconazole; and dronedarone.