Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillators: The RAID Trial
Wojciech Zareba, James P Daubert, Christopher A Beck, David T Huang, Jeffrey D Alexis, Mary W Brown, Kathryn Pyykkonen, Scott McNitt, David Oakes, Changyong Feng, Mehmet K Aktas, Felix Ayala-Parades, Adrian Baranchuk, Marc Dubuc, Mark Haigney, Alexander Mazur, Craig A McPherson, L Brent Mitchell, Andrea Natale, Jonathan P Piccini, Merritt Raitt, Mayer Y Rashtian, Claudio Schuger, Stephen Winters, Seth J Worley, Ohad Ziv, Arthur J Moss, RAID Trial Investigators, W Zareba, K Pyykkonen, A Buttaccio, E Perkins, D DeGrey, S Robertson, A J Moss, M Brown, R Lansing, A Oberer, B Polonsky, V Ross, A Papernov, S Schleede, C Beck, D Oakes, C Feng, S McNitt S, W J Hall, W Zareba, A Moss, J Daubert, C Beck, M Brown, D Huang, S Winters, C Schuger, M Haigney, J Piccini, J Alexis, L Chen, A Miller, J F Richeson, S Rosero, D Huang, V Kutyifa, A Shah, G Lamas, F Cohn, F Harrell Jr, I Piña, J Poole, M Sullivan, D Lathrop, N Geller, R Boineau, J Trondell, L Cooper, E Itturiaga, R Boineau, C Gottlieb, S Greer, C Perzanowski, C McPherson, C Hedgepeth, C Assal, T Salam, I Woollett, G Tomassoni, F Ayala-Paredes, A Russo, S Punnam, R Sangrigoli, S Sloan, S Kutalek, J Piccini, A Sun, D Lustgarten, G Monir, D Haithcock, R Sorrentino, D Cannom, J Kluger, C Schuger, S Varanasi, M Rashtian, F Philippon, R Berger, M Mazzella, T Lessmeier, J Silver, S Worley, M Bernabei, D Esberg, M Dixon, P LeLorier, Y Greenberg, V Essebag, G Venkataraman, T Shinn, M Dubuc, S Winters, G Turitto, C Henrikson, M Mirro, M Raitt, A Baranchuk, G O'Neill, E Lockwood, M Vloka, J Hurwitz, R H Mead, P Somasundarum, E Aziz, E Rashba, A Budzikowski, M Cox, A Natale, E Chung, O Ziv, F McGrew 3rd, K Tamirisa, A Greenspon, M Estes, S Taylor, R Janardhanan, L B Mitchell, M Burke, M Attari, B Mikaelian, S Hsu, J Conti, A Mazur, S Shorofsky, L Rosenthal, S Sakaguchi, D Wolfe, G Flaker, S Saba, M Aktas, P Mason, A Shalaby, D Musat, R Abraham, K Ellenbogen, C Fellows, G Venkataraman, N Kavesh, G Thomas, D Hemsworth, B Williamson, Wojciech Zareba, James P Daubert, Christopher A Beck, David T Huang, Jeffrey D Alexis, Mary W Brown, Kathryn Pyykkonen, Scott McNitt, David Oakes, Changyong Feng, Mehmet K Aktas, Felix Ayala-Parades, Adrian Baranchuk, Marc Dubuc, Mark Haigney, Alexander Mazur, Craig A McPherson, L Brent Mitchell, Andrea Natale, Jonathan P Piccini, Merritt Raitt, Mayer Y Rashtian, Claudio Schuger, Stephen Winters, Seth J Worley, Ohad Ziv, Arthur J Moss, RAID Trial Investigators, W Zareba, K Pyykkonen, A Buttaccio, E Perkins, D DeGrey, S Robertson, A J Moss, M Brown, R Lansing, A Oberer, B Polonsky, V Ross, A Papernov, S Schleede, C Beck, D Oakes, C Feng, S McNitt S, W J Hall, W Zareba, A Moss, J Daubert, C Beck, M Brown, D Huang, S Winters, C Schuger, M Haigney, J Piccini, J Alexis, L Chen, A Miller, J F Richeson, S Rosero, D Huang, V Kutyifa, A Shah, G Lamas, F Cohn, F Harrell Jr, I Piña, J Poole, M Sullivan, D Lathrop, N Geller, R Boineau, J Trondell, L Cooper, E Itturiaga, R Boineau, C Gottlieb, S Greer, C Perzanowski, C McPherson, C Hedgepeth, C Assal, T Salam, I Woollett, G Tomassoni, F Ayala-Paredes, A Russo, S Punnam, R Sangrigoli, S Sloan, S Kutalek, J Piccini, A Sun, D Lustgarten, G Monir, D Haithcock, R Sorrentino, D Cannom, J Kluger, C Schuger, S Varanasi, M Rashtian, F Philippon, R Berger, M Mazzella, T Lessmeier, J Silver, S Worley, M Bernabei, D Esberg, M Dixon, P LeLorier, Y Greenberg, V Essebag, G Venkataraman, T Shinn, M Dubuc, S Winters, G Turitto, C Henrikson, M Mirro, M Raitt, A Baranchuk, G O'Neill, E Lockwood, M Vloka, J Hurwitz, R H Mead, P Somasundarum, E Aziz, E Rashba, A Budzikowski, M Cox, A Natale, E Chung, O Ziv, F McGrew 3rd, K Tamirisa, A Greenspon, M Estes, S Taylor, R Janardhanan, L B Mitchell, M Burke, M Attari, B Mikaelian, S Hsu, J Conti, A Mazur, S Shorofsky, L Rosenthal, S Sakaguchi, D Wolfe, G Flaker, S Saba, M Aktas, P Mason, A Shalaby, D Musat, R Abraham, K Ellenbogen, C Fellows, G Venkataraman, N Kavesh, G Thomas, D Hemsworth, B Williamson
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).
Keywords: implantable cardioverter-defibrillator; ranolazine; ventricular fibrillation; ventricular tachycardia.
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Source: PubMed