Safety and mortality outcomes for direct oral anticoagulants in renal transplant recipients

Abstract

Purpose Direct oral anticoagulants (DOACs) are increasingly used in renal transplant recipients (RTR), but relatively understudied in this population. We assess the safety of post-transplant anticoagulation with DOACs compared to warfarin. Methods We conducted a retrospective study of RTRs at the Mayo Clinic sites (2011-present) that were anticoagulated for greater than 3 months excluding the 1st month post-transplant. The main safety outcomes were bleeding and all-cause mortality. Concomitant antiplatelet and interacting drugs were noted. DOAC dose adjustment was assessed according to common US prescribing practices, guidelines, and/or FDA labeling. Results The median follow-up was longer for RTRs on warfarin (1098 days [IQR 521, 1517]) than DOACs (449 days [IQR 338, 942]). Largely, there were no differences in baseline characteristics and comorbidities between RTRs on DOACs (n = 208; apixaban 91.3%, rivaroxaban 8.7%) versus warfarin (n = 320). There was no difference in post-transplant use of antiplatelets, immunosuppressants, most antifungals assessed, or amiodarone. There was no significant difference in incident major bleeding (8.4 vs. 5.3%, p = 0.89), GI bleeding (4.4% vs. 1.9%, p = 0.98), or intra-cranial hemorrhage (1.9% vs. 1.4%, p = 0.85) between warfarin and DOAC. There was no significant difference in mortality in the warfarin group compared to DOACs when adjusted for follow-up time (22.2% vs. 10.1%, p = 0.21). Rates of post-transplant venous thromboembolism, atrial fibrillation or stroke were similar between the two groups. 32% (n = 67) of patients on DOACs were dose reduced, where 51% of those reductions were warranted. 7% of patients that were not dose reduced should have been. Conclusions DOACs did not have inferior bleeding or mortality outcomes compared to warfarin in RTRs. There was greater use of warfarin compared to DOACs and a high rate of improper DOAC dose reduction.