Apixaban in HVAD Patients Non-Compliant to Standard Vitamin-K-Antagonism

Abstract

Purpose Long-term outcome of patients with chronic mechanical circulatory support (MCS) depends significantly on the time in INR-Target-Range (ITTR) to prevent detrimental adverse events such as VAD thrombosis and cerebrovascular accidents (CVA). Despite intensified INR self-management and patient education, intraindividual variations preclude high ITTR in some, delineating a significant risk. Patients non-compliant to standard vitamin K antagonism (VKA) represent a therapeutic challenge with dismal outcomes. Postoperative transitioning to VKA by direct Xa inhibitors is well established. We present the outcome of patients non-compliant to VKA supported by Medtronic HVAD anticoagulated chronically with the direct Xa inhibitor Apixaban. Methods 22 HVAD-patients, aged 64,5 years (35-81) were anticoagulated by Apixaban 10 mg in combination with either 100 mg Aspirin (n=10) or 75 mg Clopidogrel (n=12) daily, controlled by multiplate testing. Non-compliance was defined as inability to apply the INR self-management reliably after 3 or more extensive trainings or the documentation of 3 or more low INR, requiring therapeutic intervention. LDH was recorded serially to detect early VAD thrombosis. Results Apixaban therapy was begun after a median of 25,5 days (3 - 1533) of standard therapy. Observational time on Apixaban ranged from 21 - 518 days (mean 263 ± 122) summing up to 5786 days. Mean time on device was 408 ± 296 days (45 - 1554). All patients tolerated the Apixaban therapy well with no compliance issues. Clinically, no signs of pump thrombosis were detected in this cohort. Plasma LDH demonstrated regular values with a mean of 210 ± 42,2U/l. Two fatal intracranial hemorrhages 127 and 513 days on Apixaban occurred, respectively, in one case according to an intracrainial aneurysmal bleeding.Overall survival in this cohort is 90,9%. Conclusion In the challenging cohort of HVAD patients non-compliant to standard VKA therapy Apixaban appears to be a safe, well tolerated and efficient therapeutic alternative. In our single center observation of 22 HVAD patients anticoagulated by Apixaban no pump thrombosis was detected with regular LDH parameter. Two fatal intracrainial bleedings occurred, in one case after a predisposing condition preoperatively.