A Trial of Complete Withdrawal of Anticoagulation Therapy in the Heartmate 3 Pump

Abstract

Summary of Objectives The HeartMate 3 Left Ventricular Assist System has demonstrated absence of confirmed de-novo pump thrombosis and reduction in stroke. However, bleeding related adverse events persist under standard anticoagulation targeting a INR range of 2.0-3.0. In an initial experience we demonstrated safety of transition to low intensity anticoagulation (INR target 1.5-1.9, n=15, follow up of at least 6 months). Whether complete cessation of anticoagulation maintains “thromboresistance” in the HeartMate 3 pump remains unknown. Methods We previously reported on a strategy of low-intensity warfarin anticoagulation in patients implanted with HeartMate 3 (J Heart Lung Transplant. 2018;37(5):579-586). Following completion of this study phase, a staged trial was approved by the single site's ethics committee and registered as NCT03704220. All patients enrolled in the low intensity warfarin study (target INR of 1.5-1.9) were considered eligible for enrollment in the “anticoagulation withdrawal” study, if they were continuing on long-term support. All patients had to meet safe eligibility criteria including pump speed reduction to facilitate aortic valve opening (to avoid root thrombus), absence of thrombus in the pre-pump cardiac system, and absence of signs of poor unloading at reduced device speed. Careful surveillance for pump thrombosis was algorithmically mandated with biomarker and serial pump log file analyses. If enrolled, they were withdrawn from warfarin therapy and followed for survival free of pump thrombosis, disabling stroke or major bleeding for at least 3 months as the primary safety end point. Endpoints Enrollment and follow up in the low intensity anticoagulation study has been reported (n=15); 13 men, mean age 57 years (18-72), with intended goal of therapy of either BTT or DT, INTERMACS Profile mean 3 (2-5), Cardiac Index mean 1.62 l/min/m2. Of 10 patients followed beyond 1 year on reduced anticoagulation, 5 patients have qualified for complete withdrawal of anticoagulation and the safety endpoint analysis will be completed prior to the ISHLT meeting in March 2019. This pivotal study is the first indication-independent anticoagulation withdrawal study in the HeartMate 3 designed to establish thrombo-resistance for the device and form the rationale for a large scale multicenter trial.