小柯机器人

圣卢克美国中部心脏研究所John A Spertus团队研究了Mavacamten治疗症状性梗阻性肥厚型心肌病的疗效。2021年5月15日，《柳叶刀》杂志发表了该成果。

改善症状是阻塞性肥厚型心肌病患者的首要治疗目标。目前可用于肥厚型心肌病的药理学选择不是疾病特异性的，且通常药效不充分或耐受性差。为了评估mavacamten（一种一流的心肌肌球蛋白抑制剂）对患者的健康状况，即症状、身体和社会功能、以及生活质量的影响，研究组在13个国家的68个临床心血管中心进行了一项临床3期、双盲、随机、安慰剂对照试验。

研究组招募症状性梗阻性肥厚型心肌病（梯度≥50 mmHg和纽约心脏病协会II-III级）的成年患者（≥18岁），将其按1：1随机分配，分别接受mavacamten或安慰剂治疗30周，然后是8周的洗脱期。患者和工作人员双盲。次要分析的主要结局是堪萨斯城心肌病问卷（KCCQ），在基线和第6周、第12周、第18周、第30周（治疗结束）和第38周（研究结束）进行评估。

2018年5月30日至2019年7月12日，共有429名成年人接受了资格评估，其中251名（59%）接受随机分配。在mavacamten组的123名患者中，有92名（75%）在基线检查和第30周完成了KCCQ；在安慰剂组的128名患者中，有88名（69%）在基线检查和第30周完成了KCCQ。

30周时，mavacamten组的KCCQ-OS评分平均增加14.9分，显著大于安慰剂组（5.4分），在所有KCCQ子量表中具有相似的益处。Mavacamten组中改善非常大（KCCQ-OS增加20分以上）的患者占36%，显著高于安慰剂组（15%），需要治疗的人数比安慰剂组减少5人。在停止治疗后，这些临床获益恢复到基线水平。

研究结果表明，与安慰剂相比，Mavacamten显著改善了有症状的梗阻性肥厚型心肌病患者的健康状况，且需要治疗的患者数量较少。

附：英文原文

Title: Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): health status analysis of a randomised, double-blind, placebo-controlled, phase 3 trial

Author: John A Spertus, Jennifer T Fine, Perry Elliott, Carolyn Y Ho, Iacopo Olivotto, Sara Saberi, Wanying Li, Chantal Dolan, Matthew Reaney, Amy J Sehnert, Daniel Jacoby

Issue&Volume: 2021-05-15

Abstract:

Background

Improving symptoms is a primary treatment goal in patients with obstructive hypertrophic cardiomyopathy. Currently available pharmacological options for hypertrophic cardiomyopathy are not disease-specific and are often inadequate or poorly tolerated. We aimed to assess the effect of mavacamten, a first-in-class cardiac myosin inhibitor, on patients' health status—ie, symptoms, physical and social function, and quality of life.

Methods

We did a health status analysis of EXPLORER-HCM, a phase 3, double-blind, randomised, placebo-controlled trial. The study took place at 68 clinical cardiovascular centres in 13 countries. Adult patients (≥18 years) with symptomatic obstructive hypertrophic cardiomyopathy (gradient ≥50 mm Hg and New York Heart Association class II–III) were randomly assigned (1:1) to mavacamten or placebo for 30 weeks, followed by an 8-week washout period. Both patients and staff were masked to study treatment. The primary outcome for this secondary analysis was the Kansas City Cardiomyopathy Questionnaire (KCCQ), a well validated disease-specific measure of patients' health status. It was administered at baseline and weeks 6, 12, 18, 30 (end of treatment), and 38 (end of study). Changes from baseline to week 30 in KCCQ overall summary (OS) score and all subscales were analysed using mixed model repeated measures. This study is registered with ClinicalTrials.gov, NCT03470545.

Findings

Between May 30, 2018, and July 12, 2019, 429 adults were assessed for eligibility, of whom 251 (59%) were enrolled and randomly assigned. Of 123 patients randomly assigned to mavacamten, 92 (75%) completed the KCCQ at baseline and week 30 and of the 128 patients randomly assigned to placebo 88 (69%) completed the KCCQ at baseline and week 30. At 30 weeks, the change in KCCQ-OS score was greater with mavacamten than placebo (mean score 14·9 [SD 15·8] vs 5·4 [13·7]; difference +9·1 [95% CI 5·5–12·8]; p<0·0001), with similar benefits across all KCCQ subscales. The proportion of patients with a very large change (KCCQ-OS ≥20 points) was 36% (33 of 92) in the mavacamten group versus 15% (13 of 88) in the placebo group, with an estimated absolute difference of 21% (95% CI 8·8–33·4) and number needed to treat of five (95% CI 3–11). These gains returned to baseline after treatment was stopped.

Interpretation

Mavacamten markedly improved the health status of patients with symptomatic obstructive hypertrophic cardiomyopathy compared with placebo, with a low number needed to treat for marked improvement. Given that the primary goals of treatment are to improve symptoms, physical and social function, and quality of life, mavacamten represents a new potential strategy for achieving these goals.

DOI: 10.1016/S0140-6736(21)00763-7

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00763-7/fulltext

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