Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillators

The RAID Trial

RAID Trial Investigators

Research output: Contribution to journalArticle

8 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

Fingerprint

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

Keywords

  • implantable cardioverter-defibrillator
  • ranolazine
  • ventricular fibrillation
  • ventricular tachycardia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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

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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)",
keywords = "implantable cardioverter-defibrillator, ranolazine, ventricular fibrillation, ventricular tachycardia",
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 D. Oakes and C. Feng and {McNitt S}, S. and Hall, {W. J.} and A. Moss and J. Daubert and D. Huang and Pina, {Ileana L.}",
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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 - Oakes, D.

AU - Feng, C.

AU - McNitt S, S.

AU - Hall, W. J.

AU - Moss, A.

AU - Daubert, J.

AU - Huang, D.

AU - Pina, Ileana L.

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)

KW - implantable cardioverter-defibrillator

KW - ranolazine

KW - ventricular fibrillation

KW - ventricular tachycardia

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U2 - 10.1016/j.jacc.2018.04.086

DO - 10.1016/j.jacc.2018.04.086

M3 - Article

VL - 72

SP - 636

EP - 645

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 6

ER -