Carmelo A Milano1, Joseph G Rogers2, Antone J Tatooles3, Geetha Bhat3, Mark S Slaughter4, Emma J Birks4, Nahush A Mokadam5, Claudius Mahr5, Jeffrey S Miller6, David W Markham6, Valluvan Jeevanandam7, Nir Uriel7, Keith D Aaronson8, Thomas A Vassiliades9, Francis D Pagani8. 1. Departments of Surgery and Medicine, Duke University School of Medicine, Durham, North Carolina. Electronic address: carmelo.milano@duke.edu. 2. Departments of Surgery and Medicine, Duke University School of Medicine, Durham, North Carolina. 3. Center for Heart Transplant and Assist Devices, Advocate Christ Medical Center, Oak Lawn, Illinois. 4. Cardiovascular and Thoracic Surgery and Department of Cardiovascular Medicine, University of Louisville, Louisville, Kentucky. 5. Divisions of Cardiothoracic Surgery and Cardiology, University of Washington, Seattle, Washington. 6. Departments of Cardiac Surgery and Medicine, St. Joseph's Hospital of Atlanta, Atlanta, Georgia. 7. Heart and Vascular Center, University of Chicago Medicine, Chicago, Illinois. 8. Divisions of Cardiovascular Medicine and Cardiothoracic Surgery, University of Michigan, Ann Arbor, Michigan. 9. Department of Clinical and Medical Affairs, Medtronic (formerly HeartWare), Framingham, Massachusetts.
Abstract
OBJECTIVES: The aim of this study was to prospectively evaluate the impact of blood pressure management on stroke rates in patients receiving the HeartWare HVAD System. BACKGROUND: The ENDURANCE trial demonstrated noninferiority of the HeartWare HVAD System versus control (HeartMate II) in patients with advanced heart failure ineligible for heart transplantation. However, stroke was more common in HVAD subjects. Post hoc analyses demonstrated increased mean arterial blood pressure as a significant independent risk factor for stroke. METHODS: The ENDURANCE Supplemental Trial was a prospective, multicenter evaluation of 465 patients with advanced heart failure ineligible for transplantation, randomized 2:1 to HVAD (n = 308) or control (n = 157). The primary endpoint was the 12-month incidence of transient ischemic attack or stroke with residual deficit 24 weeks post-event. Secondary endpoints included the composite of freedom from death, disabling stroke, and need for device replacement or urgent transplantation, as well as comparisons of stroke or transient ischemic attack rates in HVAD cohorts in ENDURANCE Supplemental and ENDURANCE. RESULTS: The enhanced blood pressure protocol significantly reduced mean arterial blood pressure. The primary endpoint was not achieved (14.7% with HVAD vs. 12.1% with control, noninferiority [margin 6%] p = 0.14). However, the secondary composite endpoint demonstrated superiority of HVAD (76.1%) versus control (66.9%) (p = 0.04). The incidence of stroke in HVAD subjects was reduced 24.2% in ENDURANCE Supplemental compared with ENDURANCE (p = 0.10), and hemorrhagic cerebrovascular accident was reduced by 50.5% (p = 0.02). CONCLUSIONS: The ENDURANCE Supplemental Trial failed to demonstrate noninferiority of HVAD versus control regarding the pre-specified primary endpoint. However, the trial confirmed that BP management is associated with reduced stroke rates in HVAD subjects. HVAD subjects, relative to control subjects, more commonly achieved the composite endpoint (freedom from death, disabling stroke, and device replacement or urgent transplantation). (A Clinical Trial to Evaluate the HeartWare™ Ventricular Assist System [ENDURANCE SUPPLEMENTAL TRIAL] [DT2]; NCT01966458).
RCT Entities:
OBJECTIVES: The aim of this study was to prospectively evaluate the impact of blood pressure management on stroke rates in patients receiving the HeartWare HVAD System. BACKGROUND: The ENDURANCE trial demonstrated noninferiority of the HeartWare HVAD System versus control (HeartMate II) in patients with advanced heart failure ineligible for heart transplantation. However, stroke was more common in HVAD subjects. Post hoc analyses demonstrated increased mean arterial blood pressure as a significant independent risk factor for stroke. METHODS: The ENDURANCE Supplemental Trial was a prospective, multicenter evaluation of 465 patients with advanced heart failure ineligible for transplantation, randomized 2:1 to HVAD (n = 308) or control (n = 157). The primary endpoint was the 12-month incidence of transient ischemic attack or stroke with residual deficit 24 weeks post-event. Secondary endpoints included the composite of freedom from death, disabling stroke, and need for device replacement or urgent transplantation, as well as comparisons of stroke or transient ischemic attack rates in HVAD cohorts in ENDURANCE Supplemental and ENDURANCE. RESULTS: The enhanced blood pressure protocol significantly reduced mean arterial blood pressure. The primary endpoint was not achieved (14.7% with HVAD vs. 12.1% with control, noninferiority [margin 6%] p = 0.14). However, the secondary composite endpoint demonstrated superiority of HVAD (76.1%) versus control (66.9%) (p = 0.04). The incidence of stroke in HVAD subjects was reduced 24.2% in ENDURANCE Supplemental compared with ENDURANCE (p = 0.10), and hemorrhagic cerebrovascular accident was reduced by 50.5% (p = 0.02). CONCLUSIONS: The ENDURANCE Supplemental Trial failed to demonstrate noninferiority of HVAD versus control regarding the pre-specified primary endpoint. However, the trial confirmed that BP management is associated with reduced stroke rates in HVAD subjects. HVAD subjects, relative to control subjects, more commonly achieved the composite endpoint (freedom from death, disabling stroke, and device replacement or urgent transplantation). (A Clinical Trial to Evaluate the HeartWare™ Ventricular Assist System [ENDURANCE SUPPLEMENTAL TRIAL] [DT2]; NCT01966458).
Authors: Jennifer A Cowger; Palak Shah; Francis D Pagani; Gillan Grafton; John Stulak; Themistokles Chamogeorgakis; David Lanfear; Hassan Nemeh; Sean Pinney Journal: J Heart Lung Transplant Date: 2019-11-26 Impact factor: 10.247
Authors: Beren Semiz; Sinan Hersek; Maziyar Baran Pouyan; Cynthia Partida; Leticia Blazquez-Arroyo; Van Selby; Georg Wieselthaler; James M Rehg; Liviu Klein; Omer T Inan Journal: IEEE J Biomed Health Inform Date: 2020-01-13 Impact factor: 5.772