Less bleeding associated with apixaban versus other direct acting oral anticoagulation in solid organ transplant recipients

Abstract

Background The purpose of this study was to evaluate outcomes of bleeding and thrombosis resulting from the use of direct oral anticoagulants (DOACs) in a large cohort of solid organ transplant (SOT) recipients. Methods This was a single center, retrospective cohort study of adult kidney, heart, lung, and liver transplant recipients transplanted between August 2009 and May 2018. Patients were stratified into two groups: those who received apixaban (apixaban group) or those patients receiving either rivaroxaban or dabigatran (non‐apixaban group). The primary endpoint was the cumulative incidence of bleeding while receiving DOAC therapy. The secondary endpoints were incidence of major bleeding and thrombosis at any time while receiving DOAC therapy. Results A total of 106 patients were included; 70 patients received apixaban and 36 patients received non‐apixaban anticoagulation. Cumulative incidence of any bleeding was lower in the apixaban group compared to the non‐apixaban group at both 90 days (4.9% vs. 16.1%) and 180 days (11.4% vs. 24.9%, P = .034). Cumulative incidence of major bleeding (P = .686) and thrombosis (P = .515) were similar between groups. DOAC dosing congruent with the package insert(s) was associated with a lower risk of thrombosis. Conclusion Apixaban‐based anticoagulation was associated with a lower cumulative incidence of any bleeding compared to non‐apixaban DOACs.

Descriptive analysis evaluating the use of direct oral anticoagulation therapy in heart and lung transplant recipients

“…A number of studies have evaluated the impact of non‐labeled dosing on bleeding and thrombotic outcomes 21,23 . Our analysis demonstrated similar rates of thrombosis and major bleeding for patients on non‐labeled dosing.…”

“…A number of studies have evaluated the impact of non-labeled dosing on bleeding and thrombotic outcomes. 21,23 Our analysis demonstrated similar rates of thrombosis and major bleeding for patients on non-labeled dosing. Of the six major bleeds in the nonlabeled dosing group, one event occurred in a patient that deviated due to an overdose from concomitant itraconazole, while the remaining patients were underdosed.…”

“…While these event rates appear higher than what is seen in landmark trials outside of the transplant population, these rates appear comparable to other transplant studies of similar size. 21,23,32 Within our analysis, concomitant hemodialysis was associated with a reduced risk of thrombosis, but a higher risk for major bleeding. This observation is likely mediated by potential accumulation of drug, resulting in a possible decreased likelihood of treatment failure and increased risk of bleeding.…”

“…also reported that patients that deviated from package labeling were at a higher risk of thrombosis with no increased risk of bleeding. 23 This study demonstrated that 42.9% of patients on apixaban and 13.9%…”

A Review of Direct-acting Oral Anticoagulants and Their Use in Solid Organ Transplantation

“…The available literature suggests that the DOACs are associated with a lower risk of bleeding than warfarin in SOT recipients; however, there is a dearth of data comparing one DOAC to another with respect to bleeding in the SOT population. Salerno et al 89 conducted a single-center, retrospective analysis evaluating the use of apixaban (n = 70) versus nonapixaban DOACs (rivaroxaban or dabigatran, n = 36) among kidney, heart, lung, and liver transplant recipients. The primary outcome evaluated was the incidence of bleeding, whereas secondary outcomes included the frequency of major bleeding episodes and thromboembolic events.…”