Safety and efficacy of direct oral anticoagulants under long‐term immunosuppressive therapy after liver, kidney and pancreas transplantation

Abstract

Summary The safety of direct oral anticoagulants (DOACs) in patients after solid organ transplantation (SOT) is not well defined. This study aimed at describing the safety and efficacy of DOACs in patients after SOT. Patients after kidney and/or liver transplantation under maintenance immunosuppression treated with rivaroxaban (n = 26), apixaban (n = 20) and edoxaban (n = 1) were included. Clinical data were collected retrospectively and using a questionnaire. DOAC plasma levels and thrombin generation (TG) were measured in patients after SOT and compared with nontransplanted controls receiving DOACs. DOACs were administered for 84.6 patient‐years. Mean immunosuppressive trough levels after DOAC initiation increased from baseline by 18.8 ± 29.6% compared to 3.0 ± 16.5% in matched controls (P = 0.004), without significant differences in dose adjustments. No transplant rejection or significant change in liver or renal function was observed. There was one major bleeding after the observation period but no thromboembolic complication. DOAC plasma levels reached the expected range in all patients. The intrinsic hemostatic activity in transplanted patients was higher compared to nontransplant controls. Treatment with DOACs after SOT is safe and effective. Immunosuppressive trough levels should be monitored after DOAC initiation, particularly in the early phase after SOT. These data should be confirmed in a prospective study.

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

“…Existing literature regarding DOAC use in RTR involves small populations, often with low bleeding events limiting conclusions on safety [ 11 , 14 – 17 ]. Other studies pool multiple transplant types, limiting interpretation of results in RTR [ 15 , 18 , 19 ].…”

The Impact of Rivaroxaban and Apixaban on Tacrolimus Trough Levels

“…Of the 20 recipients included, 6 had TAC dose adjustments after DOAC initiation complicating the interpretation of these results. 21 Conversely, a prospective study evaluating 11 heart transplant recipients did not find a significant change in TAC (n ¼ 3) or cyclosporine (n ¼ 8) troughs after initiating RIVA. 23 The aim of the current study was to further investigate whether RIVA/APIX affect TAC troughs in solid organ transplant recipients.…”

“…Within the limited available literature, there is conflicting evidence as to whether DOACs alter TAC pharmacokinetics. [20][21][22][23][24] A 22-patient subgroup analysis of a single-center, retrospective study of solid organ transplant recipients demonstrated that concomitant use of TAC and RIVA significantly increases TAC dose-adjusted trough concentration by 9.2% (P ¼ 0.042). 20 Another study observed a non-statistically significant (P ¼ 0.78) mean increase of 16.5% in TAC troughs in 20 recipients who received DOACs after transplantation.…”

Antikoagulation bei abnormer Nierenfunktion oder Dialyse

“…Bei Nierentransplantierten und VHF sollten die gleichen Therapiestandards zur SSE-Prophylaxe Anwendung finden wie Patienten mit entsprechender CKD ohne Transplantation [1]. Mögliche Interaktionen mit dem Metabolismus der Immunsuppressiva und entsprechende Indikationen zur Spiegelbestimmung sollten beachtet werden [13,14]. Deutlich limitiert ist die Datenlage zu Patienten mit einem nephrotischem Syndrom und VHF.…”