Author + information
- Received November 15, 2017
- Revision received April 25, 2018
- Accepted May 3, 2018
- Published online August 27, 2018.
- Carmelo A. Milano, MDa,∗ (, )
- Joseph G. Rogers, MDa,
- Antone J. Tatooles, MDb,
- Geetha Bhat, MD, PhDb,
- Mark S. Slaughter, MDc,
- Emma J. Birks, MB, BS, PhDc,
- Nahush A. Mokadam, MDd,
- Claudius Mahr, MDd,
- Jeffrey S. Miller, MDe,
- David W. Markham, MD, MSce,
- Valluvan Jeevanandam, MDf,
- Nir Uriel, MD, MScf,
- Keith D. Aaronson, MD, MSg,
- Thomas A. Vassiliades, MDh,
- Francis D. Pagani, MD, PhDg,
- for the ENDURANCE Investigators
- aDepartments of Surgery and Medicine, Duke University School of Medicine, Durham, North Carolina
- bCenter for Heart Transplant and Assist Devices, Advocate Christ Medical Center, Oak Lawn, Illinois
- cCardiovascular and Thoracic Surgery and Department of Cardiovascular Medicine, University of Louisville, Louisville, Kentucky
- dDivisions of Cardiothoracic Surgery and Cardiology, University of Washington, Seattle, Washington
- eDepartments of Cardiac Surgery and Medicine, St. Joseph’s Hospital of Atlanta, Atlanta, Georgia
- fHeart and Vascular Center, University of Chicago Medicine, Chicago, Illinois
- gDivisions of Cardiovascular Medicine and Cardiothoracic Surgery, University of Michigan, Ann Arbor, Michigan
- hDepartment of Clinical and Medical Affairs, Medtronic (formerly HeartWare), Framingham, Massachusetts
- ↵∗Address for correspondence:
Dr. Carmelo A. Milano, Duke University School of Medicine, 4532 Hospital South–Blue Zone, Durham, North Carolina 27710.
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)
This study was supported by Medtronic (formerly HeartWare). HeartWare (now Medtronic) sponsored this clinical trial and partnered with us in this analysis, but the authors had access to all the data and provided critical review, writing, and content control. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. John R. Teerlink, MD, served as Guest Editor for this paper.
- Received November 15, 2017.
- Revision received April 25, 2018.
- Accepted May 3, 2018.
- 2018 The Authors