Aficamten in Obstructive Hypertrophic Cardiomyopathy: A Multidomain, Patient-Level Analysis of the MAPLE-HCM Trial.

The MAPLE-HCM trial showed greater improvement in exercise capacity and secondary endpoints for aficamten monotherapy vs metoprolol monotherapy.

MAPLE-HCM试验显示，与美托洛尔单药治疗相比，阿菲卡特单药治疗在改善运动能力和次要终点方面效果更佳。

The purpose of this study was to evaluate the effects of aficamten vs metoprolol across multiple clinically relevant and patient-centric measures of disease burden in oHCM.

本研究旨在评估 aficamten 与 metoprolol 在多个临床相关和以患者为中心的 oHCM 疾病负担指标上的效果。

Methods

Patients with oHCM and left ventricular outflow tract gradient (LVOT-G) ≥30 mm Hg at rest and/or ≥50 mm Hg with Valsalva were randomly assigned to aficamten (n = 88) or metoprolol (n = 87).

患有梗阻性肥厚型心肌病（oHCM）且静息状态下左心室流出道梯度（LVOT-G）≥30 mm Hg和/或Valsalva动作后≥50 mm Hg的患者被随机分配到 aficamten 组（n = 88）或 metoprolol 组（n = 87）。

Dose titration was based on vital signs and echocardiograms.

剂量滴定基于生命体征和超声心动图。

Assessment of clinical response by treatment arm was based on improvement in multiple parameters reflecting oHCM disease burden: LVOT-G <30 mm Hg at rest and <50 mm Hg with Valsalva; ≥1 class improvement in NYHA functional class and/or ≥10-point improvement in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS); ≥50% reduction in N-terminal pro-B-type natriuretic peptide; ≥1.0 mL/kg/min increase in peak oxygen consumption (pVO2); and ≥10% reduction in left atrial volume index.

治疗组的临床反应评估基于反映oHCM疾病负担的多个参数的改善：静息时LVOT-G <30 mm Hg和Valsalva时<50 mm Hg；NYHA功能等级提高≥1级和/或堪萨斯城心肌病问卷-临床总结评分（KCCQ-CSS）提高≥10分；N末端前体B型利钠肽减少≥50%；峰值氧耗量（pVO2）增加≥1.0 mL/kg/min；左心房体积指数减少≥10%。

Clinical response was classified by number of efficacy outcomes achieved: nonresponder (none), limited (1 or 2), positive (3 or 4), or complete (all 5).

临床反应根据实现的有效结果数量进行分类：无反应者（无），有限反应者（1或2个），阳性反应者（3或4个），或完全反应者（全部5个）。

Results

Baseline characteristics were similar for both treatment groups.

两组治疗的基线特征相似。

For the overall cohort, mean age was 58 ± 13.2 years; 73 (42%) were women, 103 (70%) were in NYHA functional class II and 52 (30%) in class III, mean pVO2 was 19.9 ± 5.1 mL/kg/min, and mean KCCQ-CSS score was 66 ± 16.

在整体队列中，平均年龄为58 ± 13.2岁；73名（42%）为女性，103名（70%）处于纽约心脏病协会（NYHA）功能II级，52名（30%）处于III级，平均pVO2为19.9 ± 5.1 mL/kg/min，平均KCCQ-CSS评分为66 ± 16。

At 24 weeks, aficamten treatment was associated with greater benefits in all efficacy outcome measures, with numbers needed to treat ranging from 1.5 to 5.0 relative to metoprolol treatment.

在24周时，与美托洛尔治疗相比，Aficamten治疗在所有疗效结果指标上显示出更大的益处，治疗所需的患者数量从1.5到5.0不等。

Patients treated with aficamten were more likely to be either positive or complete responders compared with patients treated with metoprolol (78% vs 3%, respectively; P < 0.001).

接受阿非卡美特治疗的患者相较于接受美托洛尔治疗的患者，更有可能成为阳性或完全应答者（分别为78%对3%；P < 0.001）。

Conclusions

In patients with symptomatic oHCM, aficamten monotherapy led to superior and rapid treatment benefits across several clinically relevant outcome measures of disease burden compared with metoprolol.

在有症状的梗阻性肥厚型心肌病患者中，阿非卡美特单药治疗相较于美托洛尔，在多个临床相关的疾病负担结果指标上带来了优越且快速的治疗效果。

These observations support the emerging role of aficamten as monotherapy for oHCM.

这些观察结果支持了Aficamten作为梗阻性肥厚型心肌病（oHCM）单药治疗的新兴作用。

(Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM [MAPLE-HCM]; NCT05767346).

（评估Aficamten与美托洛尔琥珀酸盐相比在有症状的成年oHCM患者中的疗效和安全性的3期试验[MAPLE-HCM]; NCT05767346）。