In patients with atrial fibrillation taking non-vitamin K oral anticoagulants, some concurrently prescribed drugs increased the risk for major bleeding compared with oral anticoagulants alone, study data show.
“Non-vitamin K oral anticoagulants (NOACs) are being used more frequently because of their ease of administration and comparative efficacy compared with warfarin in reducing thromboembolism and major bleeding,” Shang-Hung Chang, MD, PhD, of the cardiovascular department at the Chang Gung Memorial Hospital, Taiwan, and colleagues wrote. “However, for patients with atrial fibrillation, NOACs still pose a major bleeding risk, which is particularly problematic when multiple morbidities, high-risk medications, polypharmacy or drug-drug interactions are present.”
Chang and colleagues used data from the National Health Insurance database in Taiwan and included 91,330 patients with nonvalvular AF (mean age, 75 years; 56% men) who were prescribed dabigatran (n = 45,347; Pradaxa, Boehringer Ingelheim), rivaroxaban (n = 54,006; Xarelto, Janssen) or apixaban (n = 12,886; Eliquis, Bristol-Myers Squibb/Pfizer) from 2012 to 2016.
The most common medications coprescribed with NOACs were atorvastatin (27.6%), diltiazem (22.7%), digoxin (22.5%) and amiodarone (21.1%).
The primary endpoint was major bleeding, defined as hospitalization or ED visit with diagnosis of intracranial hemorrhage or gastrointestinal, urogenital or other bleeding.
During 447,037 person-quarters, 4,770 major bleeding events occurred.
Compared with NOAC use alone, there was an increased adjusted incidence rate per 1,000 person-years of major bleeding with concurrent use of NOACs and amiodarone (38.09 vs. 52.04; difference, 13.94; 99% CI, 9.76-18.13), NOACs and fluconazole (102.77 vs. 241.92; difference, 138.46; 99% CI, 80.96-195.97), NOACs and rifampin (65.66 vs. 103.14; difference, 36.9; 99% CI, 1.59-72.22) and NOACs and phenytoin (56.07 vs. 108.52; difference, 52.31; 99% CI, 32.18-72.44).
The adjusted incidence rate for major bleeding was significantly lower for concurrent use of NOACs and atorvastatin, digoxin, and erythromycin or clarithromycin compared with NOAC use alone. There was no significant difference in major bleeding for concurrent use of NOACS and verapamil; diltiazem; cyclosporine; ketoconazole, itraconazole, voriconazole or parconazole; and dronedarone.
“Some specific medications advised to be avoided in NOAC users, including diltiazem and amiodarone, were frequently prescribed to patients with nonvalvular atrial fibrillation in the clinical settings. ... [A]miodarone, fluconazole, rifampin and phenytoin were associated with a significantly increased risk of major bleeding, whereas some combinations not recommended by guidelines were not associated with major bleeding,” the researchers wrote.
“Physicians prescribing NOAC medications should consider the potential risks associated with concomitant use of other drugs,” Chang and colleagues wrote. by Cassie Homer
Disclosures: The authors report no relevant financial disclosures.