Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillators: The RAID Trial

Wojciech Zareba, Department of Medicine, University of Rochester Medical Center, Rochester, New York. Electronic address: wojciech_zareba@urmc.rochester.edu.
James P. Daubert, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Christopher A. Beck, Department of Biostatistics and Computational Biology (Beck, Oakes, Feng), University of Rochester Medical Center, Rochester, New York.
David T. Huang, Department of Medicine, University of Rochester Medical Center, Rochester, New York.
Jeffrey D. Alexis, Department of Medicine, University of Rochester Medical Center, Rochester, New York.
Mary W. Brown, Department of Medicine, University of Rochester Medical Center, Rochester, New York.
Kathryn Pyykkonen, Department of Medicine, University of Rochester Medical Center, Rochester, New York.
Scott McNitt, Department of Medicine, University of Rochester Medical Center, Rochester, New York.
David Oakes, Department of Biostatistics and Computational Biology (Beck, Oakes, Feng), University of Rochester Medical Center, Rochester, New York.
Changyong Feng, Department of Biostatistics and Computational Biology (Beck, Oakes, Feng), University of Rochester Medical Center, Rochester, New York.
Mehmet K. Aktas, Department of Medicine, University of Rochester Medical Center, Rochester, New York.
Felix Ayala-Parades, Faculte de Medicine, Centre Hospitalier Universitaire de Sherbrooke, Universite de Sherbrooke, Sherbrooke, Canada.
Adrian Baranchuk, Division of Cardiology, Queen's University, Kingston, Canada.
Marc Dubuc, Department of Medicine, Clinical Electrophysiology Service, Montreal Heart Institute, Montreal, Canada.
Mark Haigney, Division of Cardiology, Clinical Electrophysiology Service, F. Edward Herbert School of Medicine, Bethesda, Maryland.
Alexander Mazur, Division of Cardiovascular Medicine, University of Iowa, Iowa City, Iowa.
Craig A. McPherson, Cardiology Section, Bridgeport Hospital, Bridgeport, Connecticut.
L Brent Mitchell, Division of Cardiology, University of Calgary, Calgary, Canada.
Andrea Natale, Texas Cardiac Arrhythmia Research Foundation, Austin, Texas.
Jonathan P. Piccini, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Merritt Raitt, Division of Cardiology, VA Portland Health Care System and Knight Cardiovascular Institute, Oregon Health and Sciences University, Portland VA Medical Center, Portland, Oregon.
Mayer Y. Rashtian, Department of Cardiology, Huntington Memorial Hospital, Pasadena, California.
Claudio Schuger, Division of Cardiology, Henry Ford Hospital, Detroit, Michigan.
Stephen Winters, Department of Cardiovascular Medicine, Morristown Medical Center, Morristown, New Jersey.
Seth J. Worley, Cardiac Rhythm Device Management, MedStar Heart and Vascular Institute, Washington Hospital Center, Washington, DC.
Ohad Ziv, Heart and Vascular Center, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio.

Document Type

Article

Publication Title

Journal of the American College of Cardiology

Abstract

BACKGROUND: Ventricular tachycardia (VT) and ventricular fibrillation (VF) remain a challenging problem in patients with implantable cardioverter-defibrillators (ICDs). OBJECTIVES: This study aimed to determine whether ranolazine administration decreases the likelihood of VT, VF, or death in patients with an ICD. METHODS: This was double-blind, placebo-controlled clinical trial in which high-risk ICD patients with ischemic or nonischemic cardiomyopathy were randomized to 1,000 mg ranolazine twice a day or placebo. The primary endpoint was VT or VF requiring appropriate ICD therapy or death, whichever occurred first. Pre-specified secondary endpoints included ICD shock for VT, VF, or death and recurrent VT or VF requiring ICD therapy. RESULTS: Among 1,012 ICD patients (510 randomized to ranolazine and 502 to placebo) the mean age was 64 ± 10 years and 18% were women. During 28 ± 16 months of follow-up there were 372 (37%) patients with primary endpoint, 270 (27%) patients with VT or VF, and 148 (15%) deaths. The blinded study drug was discontinued in 199 (39.6%) patients receiving placebo and in 253 (49.6%) patients receiving ranolazine (p = 0.001). The hazard ratio for ranolazine versus placebo was 0.84 (95% confidence interval: 0.67 to 1.05; p = 0.117) for VT, VF, or death. In a pre-specified secondary analysis, patients randomized to ranolazine had a marginally significant lower risk of ICD therapies for recurrent VT or VF (hazard ratio: 0.70; 95% confidence interval: 0.51 to 0.96; p = 0.028). There were no other significant treatment effects in other pre-specified secondary analyses, which included individual components of the primary endpoint, inappropriate shocks, cardiac hospitalizations, and quality of life. CONCLUSIONS: In high-risk ICD patients, treatment with ranolazine did not significantly reduce the incidence of the first VT or VF, or death. However, the study was underpowered to detect a difference in the primary endpoint. In prespecified secondary endpoint analyses, ranolazine administration was associated with a significant reduction in recurrent VT or VF requiring ICD therapy without evidence for increased mortality. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253).

First Page

636

Last Page

645

DOI

10.1016/j.jacc.2018.04.086

Publication Date

8-7-2018

Identifier

30071993 (pubmed); 10.1016/j.jacc.2018.04.086 (doi); S0735-1097(18)35075-7 (pii)

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