Cardiovascular Division, Department of Medicine, (S.C., R.G.B.), Washington University School of Medicine, St Louis, MO.
Department of Genetics (S.C.), Washington University School of Medicine, St Louis, MO.
Circulation. 2024 Feb 13;149(7):498-509. doi: 10.1161/CIRCULATIONAHA.123.065600. Epub 2023 Nov 14.
Compared with men, women with hypertrophic cardiomyopathy (HCM) have a higher incidence of heart failure and worse outcomes. We investigated baseline clinical and echocardiographic characteristics and response to mavacamten among women compared with men in the EXPLORER-HCM study (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy).
A prespecified post hoc analysis of sex from the blinded, randomized EXPLORER-HCM trial of mavacamten versus placebo in symptomatic patients with obstructive HCM was performed. Baseline characteristics were compared with tests for continuous variables (expressed as mean values) and χ tests for categorical variables. Prespecified primary, secondary, and exploratory end points and echocardiographic measurements from baseline to end of treatment (week 30) were analyzed with ANCOVA for continuous end points and a generalized linear model with binomial distribution for binary end points, with adjustment for each outcome's baseline value, New York Heart Association class, β-blocker use, and ergometer type.
At baseline, women (n=102) were older (62 years versus 56 years; <0.0001), had lower peak oxygen consumption (16.7 mL·kg·min versus 21.3 mL·kg·min; <0.0001), were more likely to be assigned New York Heart Association class III (42% versus 17%; <0.0001), had worse health status (Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score 64 versus 75; <0.0001), and had higher baseline plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels (1704 ng/L versus 990 ng/L; =0.004) than men (n=149). After 30 weeks of mavacamten treatment, similar improvements were observed in women and men in the primary composite end point (percentage difference on mavacamten versus placebo, 22% versus 19%, respectively; =0.759) and in the secondary end points of change in postexercise left ventricular outflow tract gradient (-42.4 mm Hg versus -33.6 mm Hg; =0.348), change in peak oxygen consumption (1.2 mL·kg·min versus 1.6 mL·kg·min; =0.633), and percentage achieving ≥1 New York Heart Association class improvement (41% versus 28%; =0.254). However, women had greater improvement in health status (Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score 14.8 versus 6.1; =0.026) and in the exploratory end point of NT-proBNP levels (-1322 ng/L versus -649 ng/L; =0.0008).
Although at baseline women with symptomatic obstructive HCM enrolled in EXPLORER-HCM were older and had worse heart failure and health status than men, treatment with mavacamten resulted in similar improvements in the primary and most secondary EXPLORER-HCM end points and greater improvements in health status and NT-proBNP.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03470545.
与男性相比，患有肥厚型心肌病（HCM）的女性心力衰竭发生率更高，结局更差。我们研究了女性与男性相比在 EXPLORER-HCM 研究中的基线临床和超声心动图特征以及对马卡塞特治疗的反应。
对马卡塞特治疗有症状梗阻性肥厚型心肌病患者的 EXPLORER-HCM 试验的盲法、随机对照部分进行了预先设定的性别后分析。连续变量（表示为平均值）采用 t 检验，分类变量采用卡方检验进行比较。采用协方差分析比较主要、次要和探索性终点以及基线至治疗结束（第 30 周）的超声心动图测量值，二项分布的广义线性模型用于连续终点，调整每个结局的基线值、纽约心脏协会心功能分级、β受体阻滞剂的使用和测力计类型。
基线时，女性（n=102）年龄较大（62 岁 vs 56 岁；<0.0001），峰值耗氧量较低（16.7 mL·kg·min vs 21.3 mL·kg·min；<0.0001），更有可能被分配为纽约心脏协会心功能分级 III 级（42% vs 17%；<0.0001），健康状况更差（堪萨斯城心肌病问卷临床概要评分 64 分 vs 75 分；<0.0001），基线时血浆 N 末端 B 型利钠肽前体（NT-proBNP）水平较高（1704 ng/L vs 990 ng/L；=0.004）。马卡塞特治疗 30 周后，女性和男性在主要复合终点（马卡塞特与安慰剂的百分比差异，分别为 22% vs 19%；=0.759）和次要终点（运动后左心室流出道梯度的变化[-42.4 mm Hg 与-33.6 mm Hg；=0.348]）、峰值耗氧量的变化（1.2 mL·kg·min 与 1.6 mL·kg·min；=0.633）和达到≥1 个纽约心脏协会心功能分级改善的百分比（41%与 28%；=0.254）方面均观察到相似的改善。然而，女性的健康状况（堪萨斯城心肌病问卷临床概要评分 14.8 分 vs 6.1 分；=0.026）和探索性终点 NT-proBNP 水平（-1322 ng/L 与-649 ng/L；=0.0008）的改善更大。
尽管在 EXPLORER-HCM 中纳入的有症状梗阻性肥厚型心肌病的女性基线时年龄较大且心力衰竭和健康状况较男性差，但马卡塞特治疗可使主要和大多数次要 EXPLORER-HCM 终点得到相似改善，并使健康状况和 NT-proBNP 得到更大改善。
