阿非坎顿治疗症状性非梗阻性肥厚型心肌病的有效性和安全性：REDWOOD-HCM试验第4队列的结果。

IF 6.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of Cardiac Failure Pub Date : 2024-11-01 DOI:10.1016/j.cardfail.2024.02.020

AHMAD MASRI MD, MS , MARK V. SHERRID MD , THEODORE P. ABRAHAM MD , LUBNA CHOUDHURY MD, MRCPI , PABLO GARCIA-PAVIA MD, PhD , CHRISTOPHER M. KRAMER MRCPI , ROBERTO BARRIALES-VILLA MD, PhD , ANJALI T. OWENS MD , FLORIAN RADER MD , SHERIF F. NAGUEH MD , IACOPO OLIVOTTO MD , SARA SABERI MD , ALBREE TOWER-RADER MD , TIMOTHY C. WONG MD , CAROLINE J. COATS MD, PhD , HUGH WATKINS MD, PhD , MICHAEL A. FIFER MD , SCOTT D. SOLOMON MD , STEPHEN B. HEITNER MD , DANIEL L. JACOBY MD , MARTIN S. MARON MD

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引用次数: 0

摘要

背景这项开放标签的2期试验评估了非卡坦治疗非梗阻性肥厚型心肌病（nHCM）患者的安全性和有效性：有症状的nHCM患者（左心室流出道阻塞梯度≤30 mmHg、左心室射血分数[LVEF]≥60%、N末端前B型钠尿肽[NT-proBNP]>300 pg/mL）接受阿菲康坦治疗，每日一次，每次5-20 mg（根据超声心动图LVEF调整剂量），为期10周：41名患者（平均± SD年龄为56±16岁；59%为女性）入组。第 10 周时，22 名患者（55%）的纽约心脏协会分级≥1 级；11 名患者（29%）无症状。22名（55%）患者的堪萨斯城心肌病问卷临床总分有了临床意义上的改善。症状缓解的同时，NT-proBNP（56%；P < 0.001）和高敏心肌肌钙蛋白 I（22%；P < 0.005）也有所下降。观察到 LVEF 略有降低（平均值 ± SD），从 -5.4% ± 10 降至 64.6% ± 9.1。结论：对有症状的 nHCM 患者使用阿菲康坦总体上是安全的，并能改善心衰症状和心脏生物标志物：试验注册：ClinicalTrials.gov Identifier：NCT04219826 摘要：非阻塞性肥厚型心肌病（nHCM）是一种心肌异常增厚的疾病。目前尚无成熟的药物疗法。Aficamten 是一种新型心肌肌球蛋白抑制剂，旨在针对肥厚性心肌病的根本原因进行治疗。REDWOOD-HCM Cohort 4 是探索阿菲康坦对有 nHCM 症状的患者的疗效和安全性的第一项研究。大多数患者的健康状况和功能状态都有所改善。血液中表明心脏压力过大和心肌细胞受损的生物标志物水平也明显下降。这些结果支持对 nHCM 患者进行更大规模的安慰剂对照研究（ACACIA-HCM）。

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Efficacy and Safety of Aficamten in Symptomatic Nonobstructive Hypertrophic Cardiomyopathy: Results From the REDWOOD-HCM Trial, Cohort 4

Background

This open-label phase 2 trial evaluated the safety and efficacy of aficamten in patients with nonobstructive hypertrophic cardiomyopathy (nHCM).

Methods

Patients with symptomatic nHCM (left ventricular outflow tract obstruction gradient ≤ 30 mmHg, left ventricular ejection fraction [LVEF] ≥ 60%, N-terminal pro-B-type natriuretic peptide [NT-proBNP] > 300 pg/mL) received aficamten 5–15 mg once daily (doses adjusted according to echocardiographic LVEF) for 10 weeks.

Results

We enrolled 41 patients (mean ± SD age 56 ± 16 years; 59% female). At Week 10, 22 (55%) patients experienced an improvement of ≥ 1 New York Heart Association class; 11 (29%) became asymptomatic. Clinically relevant improvements in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores occurred in 22 (55%) patients. Symptom relief was paralleled by reductions in NT-proBNP levels (56%; P < 0.001) and high-sensitivity cardiac troponin I (22%; P < 0.005). Modest reductions in LVEF (mean ± SD) of −5.4% ± 10 to 64.6% ± 9.1 were observed. Three (8%) patients had asymptomatic reduction in LVEF < 50% (range: 41%–48%), all returning to normal after 2 weeks of washout. One patient with prior history of aborted sudden cardiac death experienced a fatal arrhythmia during the study.

Conclusions

Aficamten administration for symptomatic nHCM was generally safe and was associated with improvements in heart failure symptoms and cardiac biomarkers.

Trial registration

ClinicalTrials.gov Identifier: NCT04219826

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来源期刊

Journal of Cardiac Failure 医学-心血管系统

CiteScore

7.80

自引率

8.30%

发文量

653

审稿时长

21 days

期刊介绍： Journal of Cardiac Failure publishes original, peer-reviewed communications of scientific excellence and review articles on clinical research, basic human studies, animal studies, and bench research with potential clinical applications to heart failure - pathogenesis, etiology, epidemiology, pathophysiological mechanisms, assessment, prevention, and treatment.