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

    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 C. Feng and {McNitt S}, S. and Hall, {W. J.} and A. Moss and J. Daubert and D. Huang and S. Winters and Charles Henrikson",
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    language = "English (US)",
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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 - Feng, C.

    AU - McNitt S, S.

    AU - Hall, W. J.

    AU - Moss, A.

    AU - Daubert, J.

    AU - Huang, D.

    AU - Winters, S.

    AU - Henrikson, Charles

    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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    DO - 10.1016/j.jacc.2018.04.086

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    JO - Journal of the American College of Cardiology

    JF - Journal of the American College of Cardiology

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