Risk of major bleeding associated with concomitant use of anticancer drugs and direct oral anticoagulant in patients with cancer and atrial fibrillation

This study evaluated the risk of major bleeding associated with concomitant use of direct oral anticoagulant (DOAC) and anticancer drugs (ACDs), which share metabolic pathways, in patients with atrial fibrillation (AF) and cancer. We performed a retrospective cohort study using Taiwan’s National Health Insurance database and included patients with AF and cancer who received DOAC prescriptions from 1 to 2012 to 31 December 2017. The incidence of major bleeding in person-quarters with concomitant use of DOAC and any of 15 ACDs with inhibitory or competitive effects of CYP3A4 or P-gp activity (docetaxel, vinorelbine, methotrexate, irinotecan, etoposide, doxorubicin, cyclophosphamide, imatinib, nilotinib, abiraterone, bicalutamide, tamoxifen, anastrozole, cyclosporine, tacrolimus) was compared with that in person-quarters with DOAC alone. Adjusted incidence-rate differences between DOAC use with and without concurrent ACDs were estimated using Poisson regression models weighted by the inverse probability of treatment. In 13,158 patients with AF and cancer (76.9 ± 8.9 years; male 60%), 1545 major bleeding events occurred during 90,540 DOAC-exposed person-quarters. Concurrent use of DOAC and any of 15 ACDs occurred in only 18% of patients. Compared with use of DOAC alone, concomitant use of DOAC and these ACDs was not associated with an increased risk of major bleeding. Co-medication with DOAC and ACDs with inhibitory or competitive effects on CYP3A4 or P-gp activity was not associated with a higher risk of major bleeding than DOAC alone. Our findings may provide clinicians with confidence regarding the safety of concurrent use of DOAC and ACDs in patients with AF and cancer.