Immune modulating drugs and oral anticoagulation in kidney transplant recipients: comparison of direct oral anticoagulants versus antagonist of vitamin-k. results from a multicenter prospective study

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Background direct oral anticoagulants (DOACs) are a well-known alternative to conventional antagonist of vitamin-K (avK) and have emerged as the preferred choice due to their safety and efficacy profile. However, immune modulating drugs as cyclosporine and tacrolimus, commonly used for transplant recipients, may interfere with DOACs. Aim of this study: evaluate safety and efficacy profile of direct oral anticoagulants (DOACs) compared to warfarin in kidney transplant recipients (KTRs) treated with immune modulating agents. Methods a multi-center study from 4 Italian hospitals enrolling KTRs on DOACs or avK was carried out. Sixty-nine patients on DOACs were compared with fifty patients on avK with mean estimated glomerular filtrate rate (eGFR) > 45 mL/min. Clinical follow-up and serial evaluation of renal function and serum levels of immune modulating drugs during 24 months follow-up (FU) was performed. Results Mean age of DOACs patients was 67±9 and mean eGFR was57±20 mL/min. Immune-modulating therapy included tacrolimus (n=47, 71%), cyclosporin (n=13, 20%), everolimus (n=10, 7%) and sirolimus (n=4, 6%). There were no changes in Tacrolimus and Cyclosporin serum levels following 14 days therapy with DOACs (+0.5 ±2 and +28 ±31, p=0.52, 0.90, respectively) and only a patient treated with dabigatran 150 mg required a dose adjustment. Levels of Tacrolimus and cyclosporin were stable at serial evaluation during follow-up. At long-term follow-up, there were no thromboembolic events among patients treated with DOACs or avK and no differences in term of mayor bleeding (5.8% vs 4% p=0.99). There was no difference in term of eGFR decline from start therapy to 24 months FU between DOACs or avK therapy (-3.9±1 vs -3.8±2 p=0.82) (FIGURE 1). Conclusion DOACs are a potential therapeutic option among patients with kidney transplant recipients treated with immune modulating drugs. Careful evaluation of immunomodulating agent levels during the first two week of therapy should be recommended. No difference in term of bleeding, renal function decline was found when comparing with avK therapy.