Wojciech Zareba1, James P Daubert2, Christopher A Beck3, David T Huang4, Jeffrey D Alexis4, Mary W Brown4, Kathryn Pyykkonen4, Scott McNitt4, David Oakes3, Changyong Feng3, Mehmet K Aktas4, Felix Ayala-Parades5, Adrian Baranchuk6, Marc Dubuc7, Mark Haigney8, Alexander Mazur9, Craig A McPherson10, L Brent Mitchell11, Andrea Natale12, Jonathan P Piccini2, Merritt Raitt13, Mayer Y Rashtian14, Claudio Schuger15, Stephen Winters16, Seth J Worley17, Ohad Ziv18, Arthur J Moss4. 1. Department of Medicine, University of Rochester Medical Center, Rochester, New York. Electronic address: wojciech_zareba@urmc.rochester.edu. 2. Department of Medicine, Duke University Medical Center, Durham, North Carolina. 3. Department of Biostatistics and Computational Biology (Beck, Oakes, Feng), University of Rochester Medical Center, Rochester, New York. 4. Department of Medicine, University of Rochester Medical Center, Rochester, New York. 5. Faculte de Medicine, Centre Hospitalier Universitaire de Sherbrooke, Universite de Sherbrooke, Sherbrooke, Canada. 6. Division of Cardiology, Queen's University, Kingston, Canada. 7. Department of Medicine, Clinical Electrophysiology Service, Montreal Heart Institute, Montreal, Canada. 8. Division of Cardiology, Clinical Electrophysiology Service, F. Edward Herbert School of Medicine, Bethesda, Maryland. 9. Division of Cardiovascular Medicine, University of Iowa, Iowa City, Iowa. 10. Cardiology Section, Bridgeport Hospital, Bridgeport, Connecticut. 11. Division of Cardiology, University of Calgary, Calgary, Canada. 12. Texas Cardiac Arrhythmia Research Foundation, Austin, Texas. 13. Division of Cardiology, VA Portland Health Care System and Knight Cardiovascular Institute, Oregon Health and Sciences University, Portland VA Medical Center, Portland, Oregon. 14. Department of Cardiology, Huntington Memorial Hospital, Pasadena, California. 15. Division of Cardiology, Henry Ford Hospital, Detroit, Michigan. 16. Department of Cardiovascular Medicine, Morristown Medical Center, Morristown, New Jersey. 17. Cardiac Rhythm Device Management, MedStar Heart and Vascular Institute, Washington Hospital Center, Washington, DC. 18. Heart and Vascular Center, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio.
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 receivingplacebo 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).
RCT Entities:
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 ICDpatients 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 ICDpatients (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 ICDpatients, 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).
Authors: Craig R Narins; Mehmet K Aktas; Anita Y Chen; Scott McNitt; Fred S Ling; Arwa Younis; Wojciech Zareba; James P Daubert; David T Huang; Spencer Rosero; Valentina Kutyifa; Ilan Goldenberg Journal: JACC Clin Electrophysiol Date: 2021-08-25
Authors: Arwa Younis; Ilan Goldenberg; Shamroz Farooq; Hagai Yavin; James Daubert; Merritt Raitt; Alexander Mazur; David T Huang; Brent L Mitchell; Mayer R Rashtian; Stephen Winters; Margot Vloka; Mehmet Aktas; Matthew A Bernabei; Christopher A Beck; Scott McNitt; Wojciech Zareba Journal: JACC Clin Electrophysiol Date: 2022-04-27
Authors: Anh Tuan Ton; William Nguyen; Katrina Sweat; Yannick Miron; Eduardo Hernandez; Tiara Wong; Valentyna Geft; Andrew Macias; Ana Espinoza; Ky Truong; Lana Rasoul; Alexa Stafford; Tamara Cotta; Christina Mai; Tim Indersmitten; Guy Page; Paul E Miller; Andre Ghetti; Najah Abi-Gerges Journal: Sci Rep Date: 2021-06-08 Impact factor: 4.379
Authors: Mehmet K Aktaş; Arwa Younis; Wojciech Zareba; Valentina Kutyifa; Helmut Klein; James P Daubert; Mark Estes; Scott McNitt; Bronislava Polonsky; Ilan Goldenberg Journal: J Am Coll Cardiol Date: 2021-05-25 Impact factor: 27.203