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

RAID Trial Investigators

Research output: Contribution to journalArticle

9 Citations (Scopus)

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)

Original languageEnglish (US)
Pages (from-to)636-645
Number of pages10
JournalJournal of the American College of Cardiology
Volume72
Issue number6
DOIs
StatePublished - Aug 7 2018

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Defibrillators
Implantable Defibrillators
Ventricular Fibrillation
Ventricular Tachycardia
Placebos
Shock
Ranolazine
Therapeutics
Confidence Intervals
Controlled Clinical Trials
Cardiomyopathies
Hospitalization
Quality of Life

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

@article{bc39c195a0eb41c099bd18def14f5ba3,
title = "Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillators: The RAID Trial",
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)",
author = "{RAID Trial Investigators} and Wojciech Zareba and Daubert, {James P.} and Beck, {Christopher A.} and Huang, {David T.} and Alexis, {Jeffrey D.} and Brown, {Mary W.} and Kathryn Pyykkonen and Scott McNitt and David Oakes and Changyong Feng and Aktas, {Mehmet K.} and Felix Ayala-Parades and Adrian Baranchuk and Marc Dubuc and Mark Haigney and Alexander Mazur and McPherson, {Craig A.} and Mitchell, {L. Brent} and Andrea Natale and Piccini, {Jonathan P.} and Merritt Raitt and Rashtian, {Mayer Y.} and Claudio Schuger and Stephen Winters and Worley, {Seth J.} and Ohad Ziv and Moss, {Arthur J.} and W. Zareba and K. Pyykkonen and A. Buttaccio and E. Perkins and D. DeGrey and S. Robertson and Moss, {A. J.} and M. Brown and R. Lansing and A. Oberer and B. Polonsky and V. Ross and A. Papernov and S. Schleede and C. Beck and C. Feng and {McNitt S}, S. and Hall, {W. J.} and A. Moss and J. Daubert and D. Huang and S. Winters and C. Schuger",
year = "2018",
month = "8",
day = "7",
doi = "10.1016/j.jacc.2018.04.086",
language = "English (US)",
volume = "72",
pages = "636--645",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier USA",
number = "6",

}

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

In: Journal of the American College of Cardiology, Vol. 72, No. 6, 07.08.2018, p. 636-645.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillators

T2 - The RAID Trial

AU - RAID Trial Investigators

AU - Zareba, Wojciech

AU - Daubert, James P.

AU - Beck, Christopher A.

AU - Huang, David T.

AU - Alexis, Jeffrey D.

AU - Brown, Mary W.

AU - Pyykkonen, Kathryn

AU - McNitt, Scott

AU - Oakes, David

AU - Feng, Changyong

AU - Aktas, Mehmet K.

AU - Ayala-Parades, Felix

AU - Baranchuk, Adrian

AU - Dubuc, Marc

AU - Haigney, Mark

AU - Mazur, Alexander

AU - McPherson, Craig A.

AU - Mitchell, L. Brent

AU - Natale, Andrea

AU - Piccini, Jonathan P.

AU - Raitt, Merritt

AU - Rashtian, Mayer Y.

AU - Schuger, Claudio

AU - Winters, Stephen

AU - Worley, Seth J.

AU - Ziv, Ohad

AU - Moss, Arthur J.

AU - Zareba, W.

AU - Pyykkonen, K.

AU - Buttaccio, A.

AU - Perkins, E.

AU - DeGrey, D.

AU - Robertson, S.

AU - Moss, A. J.

AU - Brown, M.

AU - Lansing, R.

AU - Oberer, A.

AU - Polonsky, B.

AU - Ross, V.

AU - Papernov, A.

AU - Schleede, S.

AU - Beck, C.

AU - Feng, C.

AU - McNitt S, S.

AU - Hall, W. J.

AU - Moss, A.

AU - Daubert, J.

AU - Huang, D.

AU - Winters, S.

AU - Schuger, C.

PY - 2018/8/7

Y1 - 2018/8/7

N2 - 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)

AB - 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)

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U2 - 10.1016/j.jacc.2018.04.086

DO - 10.1016/j.jacc.2018.04.086

M3 - Article

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EP - 645

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 6

ER -