Author + information
- Received November 30, 2017
- Revision received April 27, 2018
- Accepted April 30, 2018
- Published online July 30, 2018.
- Wojciech Zareba, MD, PhDa,∗ (, )@UofR@DCRINews@DukeHealth,
- James P. Daubert, MDb,
- Christopher A. Beck, PhDc,
- David T. Huang, MDa,
- Jeffrey D. Alexis, MDa,
- Mary W. Brown, MSa,
- Kathryn Pyykkonen, MSa,
- Scott McNitt, MSa,
- David Oakes, PhDc,
- Changyong Feng, PhDc,
- Mehmet K. Aktas, MDa,
- Felix Ayala-Parades, MD, PhDd,
- Adrian Baranchuk, MDe,
- Marc Dubuc, MDf,
- Mark Haigney, MDg,
- Alexander Mazur, MDh,
- Craig A. McPherson, MDi,
- L. Brent Mitchell, MDj,
- Andrea Natale, MDk,
- Jonathan P. Piccini, MD, MHSb,
- Merritt Raitt, MDl,
- Mayer Y. Rashtian, MDm,
- Claudio Schuger, MDn,
- Stephen Winters, MDo,
- Seth J. Worley, MDp,
- Ohad Ziv, MDq,
- Arthur J. Moss, MDa,∗,
- for the RAID Trial Investigators
- aDepartment of Medicine, University of Rochester Medical Center, Rochester, New York
- bDepartment of Medicine, Duke University Medical Center, Durham, North Carolina
- cDepartment of Biostatistics and Computational Biology (Beck, Oakes, Feng), University of Rochester Medical Center, Rochester, New York
- dFaculte de Medicine, Centre Hospitalier Universitaire de Sherbrooke, Universite de Sherbrooke, Sherbrooke, Canada
- eDivision of Cardiology, Queen’s University, Kingston, Canada
- fDepartment of Medicine, Clinical Electrophysiology Service, Montreal Heart Institute, Montreal, Canada
- gDivision of Cardiology, Clinical Electrophysiology Service, F. Edward Herbert School of Medicine, Bethesda, Maryland
- hDivision of Cardiovascular Medicine, University of Iowa, Iowa City, Iowa
- iCardiology Section, Bridgeport Hospital, Bridgeport, Connecticut
- jDivision of Cardiology, University of Calgary, Calgary, Canada
- kTexas Cardiac Arrhythmia Research Foundation, Austin, Texas
- lDivision of Cardiology, VA Portland Health Care System and Knight Cardiovascular Institute, Oregon Health and Sciences University, Portland VA Medical Center, Portland, Oregon
- mDepartment of Cardiology, Huntington Memorial Hospital, Pasadena, California
- nDivision of Cardiology, Henry Ford Hospital, Detroit, Michigan
- oDepartment of Cardiovascular Medicine, Morristown Medical Center, Morristown, New Jersey
- pCardiac Rhythm Device Management, MedStar Heart and Vascular Institute, Washington Hospital Center, Washington, DC
- qHeart and Vascular Center, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio
- ↵∗Address for correspondence:
Dr. Wojciech Zareba, Heart Research Follow-up Program, University of Rochester Medical Center, 265 Crittenden Boulevard, CU 420653, Rochester, New York 14642-0653.
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)
↵∗ Dr. Arthur Moss passed away during resubmission of this paper.
This study was supported by grants from the National Heart, Lung, and Blood Institute: Clinical Coordination Center (Grant No. UO1 HL096607; PI: Dr. Zareba) and Data Coordination Center (Grant No. UO1 HL096610; PI: Dr. Moss). Study drug and additional financial support for drug distribution was provided by Gilead Sciences grant no. IN-US-259-0125 (to Dr. Zareba). Dr. Zareba has received research grant support from Gilead Sciences, Boston Scientific, and Zoll. Dr. Daubert has received research grant support from Biosense Webster, Gilead Sciences, Medtronic, Zoll, and St. Jude Medical; and has served as a consultant or on Speakers Bureau for the American College of Cardiology, ARCA Biopharma, Biosense Webster, Biotronik, Boston Scientific, Cardiofocus, Gilead Sciences, Medtronic, Northwestern University, Zoll, St. Jude, and Vytronus. Dr. Alexis has served on the clinical events committee for Gilead Sciences. Dr. Aktas has received research grant support from Boston Scientific and Medtronic. Dr. Mitchell has received research grant support from Boehringer Ingelheim and consulting fees from Boehringer Ingelheim, Bayer, and the BMS-Pfizer Alliance, Medtronic Inc., and Servier. Dr. Natale has served as a consultant for and received consulting honoraria from Biosense Webster, BSCI, St. Jude/Abbott, St. Jude Medical, Boston Scientific, Medtronic, and Itamar. Dr. Piccini has received research grant support from Gilead Sciences, St. Jude Medical, Spectranetics, ARCA Biopharma, Johnson & Johnson, Boston Scientific, Abbott, and Medtronic; and consulting fees from Medtronic, Sanofi, Bayer, Allergan, and Philips. Dr. Schuger has received research grants from Boston Scientific. Dr. Worley has received royalties from Merit Medical & Pressure Products; and consulting fees from Merit and Abbott. Dr. Moss has received researched grants from Gilead Sciences and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received November 30, 2017.
- Revision received April 27, 2018.
- Accepted April 30, 2018.
- 2018 The Authors