(1) - HeartWare HVAD for the Treatment of Patients With Advanced Heart Failure Ineligible for Cardiac Transplantation: Results of the ENDURANCE Destination Therapy Trial

Abstract

Mechanically assisted circulation with the HeartMate II (HMII, Thoratec®) axial flow left ventricular assist device (LVAD) has been established as a viable option for the treatment of advanced heart failure in patients ineligible for heart transplantation. The HeartWare® centrifugal flow ventricular assist device system (HVAD) is currently approved for bridge to transplant in the US. The purpose of this study, which was sponsored by HeartWare®, was to compare the safety and effectiveness of the HVAD to HMII in patients with advanced heart failure ineligible for heart transplantation. ENDURANCE was a prospective, multicenter evaluation of 450 patients with NYHA Class IIIB-IV symptoms randomized 2:1 to HVAD or HMII. Patients were adults with an ejection fraction ≤25% despite treatment with optimal medical therapy for ≥45 days or treatment with intravenous inotropes for ≥14 days or an intra-aortic balloon pump for ≥7 days. Exclusion criteria included significant end-organ dysfunction, recent myocardial infarction or stroke, coagulopathy, or an anticipated need for a right ventricular assist device. The primary endpoint was stroke free survival at two years defined as alive on the originally implanted device, transplanted or explanted for recovery without a disabling stroke (modified Rankin score >4). Treatment failure was defined as subject death, stroke with a residual modified Rankin score >4, or device malfunction or failure requiring exchange, explantation, or urgent transplantation within the first two years of support. ENDURANCE was designed and powered to demonstrate non-inferiority of the HVAD. Protocol-driven 24 month follow-up has recently been completed in 450 patients and the data is currently being locked and analyzed. Primary endpoint data will be presented in a late-breaking clinical trial session. This large, randomized clinical trial of the HVAD as mechanical circulatory support for patients ineligible for heart transplantation represents the initial clinical experience supporting this patient population.