Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillators The RAID Trial
Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillators The RAID Trial
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DOI：
10.1016/j.jacc.2018.04.086
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发表时间：
2018-08-07
影响因子：
24
通讯作者：
Moss, Arthur J.
中科院分区：
文献类型：
--
作者：
Zareba, Wojciech;Daubert, James P.;Moss, Arthur J.
背景室性心动过速（VT）和心室纤维性颤动（VF）仍然是植入式心律转复器（ICD）患者面临的一个挑战性问题。一项安慰剂对照临床试验，在该试验中，患有缺血性或非缺血性心肌病的高危ICD患者被随机分配至1，000 mg雷诺嗪每日两次或安慰剂组。主要终点是需要适当ICD治疗的VT或VF或死亡，以先发生者为准。预先规定的次要终点包括ICD电击VT，VF，或死亡和复发性VT或VF需要ICD therapy.Results在1,012 ICD患者（510随机雷诺嗪和502安慰剂）的平均年龄为64 +/- 10岁，18%是女性。在28 ± 16个月的随访期间，有372例（37%）患者达到主要终点，270例（27%）患者发生VT或VF，148例（15%）患者死亡。199例（39.6%）接受安慰剂治疗的患者和253例（49.6%）接受雷诺嗪治疗的患者停用盲态研究药物（p = 0.001）。雷诺嗪与安慰剂相比，VT、VF或死亡的风险比为0.84（95%置信区间：0.67 - 1.05; p = 0.117）。在预先指定的次要分析中，随机分配至雷诺嗪组的患者ICD治疗复发性VT或VF的风险略低（风险比：0.70; 95%置信区间：0.51至0.96; p = 0.028）。在其他预先指定的次要分析中，包括主要终点的单个组成部分，不适当的电击，心脏病住院治疗和quality of life.CONCLUSIONS在高危ICD患者中，雷诺嗪治疗并没有显著降低首次VT或VF或死亡的发生率。然而，该研究的把握度不足，无法检测主要终点的差异。在预先规定的次要终点分析中，雷诺嗪给药与需要ICD治疗的复发性VT或VF显著减少相关，没有证据表明死亡率增加。(C)2018作者由Elsevier代表美国心脏病学会基金会发布。
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 pre specified secondary endpoint analyses, ranolazine administration was associated with a significant reduction in recurrent VT or VF requiring ICD therapy without evidence for increased mortality. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.