Effect of Aficamten vs Metoprolol on Patient-Reported Health Status in Obstructive Hypertrophic Cardiomyopathy.

Given the primary treatment goal to improve patients' health status, defining the incremental benefits of aficamten over metoprolol on patients' symptoms, function, and quality of life is needed.

鉴于改善患者健康状况是主要治疗目标，因此需要明确Aficamten相较于美托洛尔在改善患者症状、功能和生活质量方面的增量益处。

In this study, the authors sought to compare patient-reported health status benefits of aficamten with metoprolol.

在这项研究中，作者试图比较患者报告的健康状况益处，将阿菲卡门特与美托洛尔进行比较。

Methods

Adults with symptomatic oHCM (Kansas City Cardiomyopathy Questionnaire [KCCQ] Clinical Summary Score [CSS] ≤90; left ventricular outflow tract obstruction ≥30 mm Hg at rest or ≥50 mm Hg with Valsalva) were randomly assigned to 24 weeks of aficamten or metoprolol as monotherapy.

被随机分配接受24周阿菲卡门特或美托洛尔单药治疗的成年症状性有症状性肥厚型心肌病患者（Kansas City Cardiomyopathy Questionnaire [KCCQ] 临床总结评分 [CSS] ≤90；静息时左心室流出道梗阻≥30毫米汞柱或Valsalva动作时≥50毫米汞柱）

Changes in KCCQ Overall Summary Score (OSS) and Seattle Angina Questionnaire Summary Score (SAQ-SS), collected serially throughout the trial, were compared between treatment groups at 24 weeks using linear regression, adjusted for randomization strata and baseline scores.

在整个试验期间，通过线性回归比较了治疗组之间在24周时的堪萨斯城心肌病问卷总体评分（KCCQ OSS）和西雅图心绞痛问卷总结评分（SAQ-SS）的变化，调整了随机分层和基线评分。

Individual participant experiences were described by comparing categories of clinically meaningful within-participant change: ≤-5 (worse), >-5 to <+5 (no change), +5 to <+10 (small improvement), +10 to <+15 (moderate improvement), +15 to <+20 (large improvement), and ≥+20 points (very large improvement).

通过比较临床意义上的参与者内变化类别来描述个体参与者体验：≤-5（恶化），>-5至<+5（无变化），+5至<+10（小幅度改善），+10至<+15（中度改善），+15至<+20（大幅度改善），以及≥+20分（非常大的改善）。

Results

Among 175 randomized patients, baseline health status scores were similar between treatment groups (n = 88 aficamten; n = 87 metoprolol).

在175名随机患者中，基线健康状况评分在治疗组之间相似（n = 88 aficamten；n = 87 metoprolol）。

Aficamten, compared with metoprolol, resulted in a greater 24-week KCCQ-OSS improvement (adjusted between-group difference: +7.8 points; 95% CI: 3.3-12.3; P < 0.001), primarily driven by a greater proportion of aficamten-treated (38.6%) vs metoprolol-treated (18.4%) patients experiencing a very large (≥20 points) KCCQ-OSS improvement (number needed to treat = 4.9; 95% CI: 3.0-13.9), and a smaller proportion experiencing worsening health status (≤-5-point change: 6.8% vs 18.4%; number needed to harm = 8.6; 95% CI: 4.7-53.3).

与美托洛尔相比，Aficamten在24周KCCQ-OSS改善方面效果更佳（调整后组间差异：+7.8分；95%置信区间：3.3-12.3；P < 0.001），主要由更大比例的Aficamten治疗患者（38.6%）与美托洛尔治疗患者（18.4%）经历了非常大的（≥20分）KCCQ-OSS改善所驱动（需要治疗人数 = 4.9；95%置信区间：3.0-13.9），以及更小比例的患者健康状况恶化（≤-5分变化：6.8% vs 18.4%；需要伤害人数 = 8.6；95%置信区间：4.7-53.3）。

Nonsignificant SAQ-SS improvements with aficamten vs metoprolol (+4.6 points; 95% CI -0.3 to 9.5 points; P = 0.063) were driven by significantly larger improvements in the SAQ Physical Limitation scale (+10.1 points; 95% CI: 3.9-16.2 points; P = 0.001).

与美托洛尔相比，阿菲卡门特在SAQ-SS评分上的改善并不显著（+4.6分；95%置信区间-0.3至9.5分；P=0.063），但这种改善主要由SAQ身体限制量表的显著更大改善所驱动（+10.1分；95%置信区间：3.9-16.2分；P=0.001）。

Conclusions

Aficamten improved the health status of patients with symptomatic oHCM significantly more than did metoprolol, highlighting its potential as an effective initial therapeutic option.

阿菲卡门特显著改善了有症状的肥厚型心肌病患者的健康状况，比美托洛尔更有效，凸显了其作为有效初始治疗选择的潜力。

(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在有症状的成人oHCM患者中的疗效和安全性的III期试验（MAPLE-HCM; NCT05767346）。