Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices

This pilot study will be a prospective, randomized, controlled, open label, trial of HeartMate 3 (HM3) LVAD patients with 1:1 randomization to either apixaban or warfarin. All patients will be treated with aspirin 81 mg daily as per the LVAD manufacturer instructions for use (IFU).

Inclusion criteria

• Patients implanted with a HeartMate 3 LVAD
• Age 18 or greater and able to provide written informed consent
• Females of childbearing age must agree to adequate contraception

Exclusion criteria

• History of post-LVAD device thrombosis, stroke, or gastrointestinal bleeding
• Patients who are bridge to transplant and a current UNOS status 1-3
• Ongoing inotrope therapy after LVAD (e.g., milrinone, dobutamine, epinephrine)
• Permanent right ventricular assist device at the time of LVAD implant
• Patients with a mechanical heart valve
• Patients with end-stage renal disease on dialysis
• Pregnant patients
• Known history of ischemic stroke, intracranial bleed, or neurosurgery within 3 months
• Known history of intracerebral arteriovenous malformation, cerebral aneurysm or mass lesions of the central nervous system.
• Recent (<48 hours) or planned spinal or epidural anesthesia or puncture
• Prior history of known thrombophilia (e.g., factor V Leiden, prothrombin gene mutation, protein C or S deficiency, antithrombin 3 deficiency, hyperhomocysteinemia, antiphospholipid antibody syndrome) or indication for higher INR goal (>2.5) with warfarin.
• Thrombolysis within the previous 7 days
• Patients with an allergy or contraindication to aspirin, warfarin, or apixaban
• Patients on antiplatelet therapy other than aspirin (e.g., clopidogrel, prasugrel, ticagrelor, dipyridamole, or pentoxifylline)
• Patients on combined P-glycoprotein and strong CPY3A4 inhibitors or inducers (e.g., fluconazole, posaconazole, rifampin)
• Known bleeding within the last 30 days requiring emergency room presentation or hospitalization
• Known history of an inherited bleeding disorder (e.g., hemophilia, von Willebrand disease)
• Patients with active bleeding or a hemoglobin < 8.0 g/dl
• Total bilirubin > 2.0 mg/dl, shock liver, hepatic encephalopathy, or biopsy proven liver cirrhosis
• INR > 2.0 not due to anticoagulation therapy
• Platelet count <100,000 cells/mm3