Amiodarone or Implantable Cardioverter-Defibrillator in Chagas Cardiomyopathy: The CHAGASICS Randomized Clinical Trial.

IF 14.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JAMA cardiology Pub Date : 2024-10-02 DOI:10.1001/jamacardio.2024.3169

Martino Martinelli-Filho, José A Marin-Neto, Mauricio Ibrahim Scanavacca, Angelo Amato Vincenzo de Paola, Paulo de Tarso Jorge Medeiros, Ruth Owen, Stuart J Pocock, Sergio Freitas de Siqueira

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引用次数: 0

Abstract

Importance: Over 10 000 people with Chagas disease experience sudden cardiac death (SCD) annually, mostly caused by ventricular fibrillation. Amiodarone hydrochloride and the implantable cardioverter-defibrillator (ICD) have been empirically used to prevent SCD in patients with chronic Chagas cardiomyopathy.

Objective: To test the hypothesis that ICD is more effective than amiodarone therapy for primary prevention of all-cause mortality in patients with chronic Chagas cardiomyopathy and moderate to high mortality risk, assessed by the Rassi score.

Design, setting, and participants: CHAGASICS is an open-label, randomized clinical trial. The study enrolled patients from 13 centers in Brazil from May 30, 2014, to August 13, 2021, with the last follow-up November 8, 2021. Patients with serological findings positive for Chagas disease, a Rassi risk score of at least 10 points (intermediate to high risk), and at least 1 episode of nonsustained ventricular tachycardia were eligible to participate. Data were analyzed from May 3, 2022, to June 16, 2023.

Interventions: Patients were randomized 1:1 to receive ICD or amiodarone (with a loading dose of 600 mg after randomization).

Main outcomes and measures: The primary outcome was all-cause mortality, and secondary outcomes included SCD, hospitalization for heart failure, and necessity of a pacemaker during the entire follow-up.

Results: The study was stopped prematurely for administrative reasons, with 323 patients randomized (166 in the amiodarone group and 157 in the ICD group), rather than the intended 1100 patients. Analysis was by intention to treat at a median follow-up of 3.6 (IQR, 1.8-4.4) years. Mean (SD) age was 57.4 (9.8) years, 185 patients (57.3%) were male, and the mean (SD) left ventricular ejection fraction was 37.0% (11.6%). There were 60 deaths (38.2%) in the ICD arm and 64 (38.6%) in the amiodarone group (hazard ratio [HR], 0.86 [95% CI, 0.60-1.22]; P = .40). The rates of SCD (6 [3.8%] vs 23 [13.9%]; HR, 0.25 [95% CI, 0.10-0.61]; P = .001), bradycardia requiring pacing (3 [1.9%] vs 27 [16.3%]; HR, 0.10 [95% CI, 0.03-0.34]; P < .001), and heart failure hospitalization (14 [8.9%] vs 28 [16.9%]; HR, 0.46 [95% CI, 0.24-0.87]; P = .01) were lower in the ICD group compared with the amiodarone arm.

Conclusions and relevance: In patients with chronic Chagas cardiomyopathy at moderate to high risk of mortality, ICD did not reduce the risk of all-cause mortality. However, ICD significantly reduced the risk of SCD, pacing need, and heart failure hospitalization compared with amiodarone therapy. Further studies are warranted to confirm the evidence generated by this trial.

Trial registration: ClinicalTrials.gov Identifier: NCT01722942.

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胺碘酮或植入式心律转复除颤器治疗恰加斯心肌病：CHAGASICS 随机临床试验。

重要性：每年有 10 000 多名南美锥虫病患者发生心脏性猝死 (SCD)，大多数是由心室颤动引起的。盐酸胺碘酮和植入式心律转复除颤器（ICD）已被经验性地用于预防慢性恰加斯心肌病患者的 SCD：目的：验证 ICD 比胺碘酮疗法更能有效预防慢性恰加斯心肌病患者全因死亡的假设：CHAGASICS是一项开放标签、随机临床试验。该研究从2014年5月30日至2021年8月13日在巴西的13个中心招募患者，最后一次随访时间为2021年11月8日。血清学检查结果为南美锥虫病阳性、拉西风险评分至少为 10 分（中高风险）、至少发生过一次非持续性室性心动过速的患者均符合参与条件。数据分析时间为2022年5月3日至2023年6月16日：患者按 1:1 随机分配接受 ICD 或胺碘酮（随机分配后负荷剂量为 600 毫克）：主要结果和测量指标：主要结果是全因死亡率，次要结果包括SCD、心衰住院以及在整个随访期间是否需要安装起搏器：由于管理方面的原因，研究提前结束，323 名患者被随机分组（胺碘酮组 166 人，ICD 组 157 人），而非预期的 1100 名患者。分析采用意向治疗，中位随访时间为 3.6（IQR，1.8-4.4）年。平均（标清）年龄为 57.4 (9.8)岁，185 名患者（57.3%）为男性，平均（标清）左心室射血分数为 37.0% (11.6%)。ICD 组有 60 人死亡（38.2%），胺碘酮组有 64 人死亡（38.6%）（危险比 [HR]，0.86 [95% CI，0.60-1.22]；P = .40）。SCD 发生率（6 [3.8%] vs 23 [13.9%]；HR，0.25 [95% CI，0.10-0.61]；P = .001）、需要起搏的心动过缓发生率（3 [1.9%] vs 27 [16.3%]；HR，0.10 [95% CI，0.03-0.34]；P 结论和意义：对于具有中度至高度死亡风险的慢性恰加斯病心肌病患者，ICD 并未降低全因死亡风险。然而，与胺碘酮疗法相比，ICD 能明显降低 SCD、起搏需求和心衰住院的风险。有必要开展进一步研究，以证实本试验所提供的证据：试验注册：ClinicalTrials.gov Identifier：NCT01722942.

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来源期刊

JAMA cardiology Medicine-Cardiology and Cardiovascular Medicine

CiteScore

45.80

自引率

1.70%

发文量

264

期刊介绍： JAMA Cardiology, an international peer-reviewed journal, serves as the premier publication for clinical investigators, clinicians, and trainees in cardiovascular medicine worldwide. As a member of the JAMA Network, it aligns with a consortium of peer-reviewed general medical and specialty publications. Published online weekly, every Wednesday, and in 12 print/online issues annually, JAMA Cardiology attracts over 4.3 million annual article views and downloads. Research articles become freely accessible online 12 months post-publication without any author fees. Moreover, the online version is readily accessible to institutions in developing countries through the World Health Organization's HINARI program. Positioned at the intersection of clinical investigation, actionable clinical science, and clinical practice, JAMA Cardiology prioritizes traditional and evolving cardiovascular medicine, alongside evidence-based health policy. It places particular emphasis on health equity, especially when grounded in original science, as a top editorial priority.