Prevention of Non-Surgical Bleeding by Management of HeartMate II Patients without Antiplatelet Therapy

PURPOSE: Optimization of antithrombotic therapy, with the goal of minimizing bleeding without adversely affecting thromboembolic (TE) rates, is a major priority of the MCS field. We evaluated the safety and efficacy of managing HeartMate II (HM II) patients without antiplatelet therapy. METHODS: Prospective, multicenter, randomized, double-blind placebo-controlled trial of aspirin (ASA) 81 mg daily in subjects ≥50 years of age receiving warfarin (INR of 2.0-2.5) after initial HM II implantation. Subjects were placed on study drug once hemodynamic stability was achieved, no later than POD 15. Primary efficacy endpoint was the composite incidence of non-surgical bleeding at 6 months. Primary safety endpoint was the composite incidence of pump thrombosis and stroke 6 months post implant. Descriptive endpoints included hemocompatibility related adverse events at 12 months. The study was stopped due to futility given competing enrollment in another study. RESULTS: 65/72 (31 placebo, 34 ASA) subjects enrolled within 48 hours of HM II implant met criteria for initiation of the study drug. At 6 and 12 months, respectively, 47 and 35 subjects remained on study drug. Study discontinuation was due to death (Placebo: 8.6% vs. ASA: 8.1%), transplant/explant (Placebo: 8.6% vs. ASA: 10.8 %), or withdrawal (Placebo: 34.3% vs. ASA: 32.4%) and was comparable between groups. In an as-treated analysis of the primary endpoints, at 6 months, the rates of nonsurgical bleeding (Placebo: 38 [21.6 - 55.9] %; ASA: 44 [27.4 - 60.8] %) and TE events (Placebo: 12.9 [1.1 - 24.7] %; ASA: 8.8 [0.0 - 18.4] %,) did not differ between groups. At 12 months, more major bleeding events had occurred in the ASA group compared to the placebo group (Placebo: 38.7 [21.6 - 55.9] %; ASA: 64.7 [48.6 - 80.8] %), but stroke rates remained comparable (Placebo: 19.4 [5.4 - 33.3] %; ASA: 20.6 [7.0 - 34.2] %). CONCLUSION: In the first prospective, randomized double blind placebo-controlled study of an ASA free regimen in patients on durable LVAD support receiving warfarin, we did not observe increased rates of TE events. Our findings are only applicable to the HMII device and significantly limited by an early study stop. However, they provide supportive rationale for the study of antiplatelet free regimen in contemporary LVADs, specifically those with decreased device thrombosis.