Mavacamten in Adolescents with Obstructive Hypertrophic Cardiomyopathy.

The efficacy and safety of mavacamten, a cardiac myosin inhibitor that is available for adults, warrant evaluation in adolescents.

对于成人可用的心脏肌球蛋白抑制剂马伐卡特，其在青少年中的有效性和安全性值得评估。

Methods

We conducted a phase 3, double-blind, randomized, placebo-controlledtrial involving symptomatic adolescents (12 to <18 years of age) with New York Heart Association class II or III obstructive hypertrophic cardiomyopathy.

我们开展了一项III期、双盲、随机、安慰剂对照试验，研究对象为患有纽约心脏病协会II级或III级梗阻性肥厚型心肌病的有症状青少年（12至<18岁）。

The patients were randomly assigned in a 1:1 ratio to receive mavacamten or placebo.

患者按照1:1的比例随机分配接受mavacamten或安慰剂治疗。

The primary end point was the change from baseline to week 28 in left ventricular outflow tract pressure gradient provoked by the Valsalva maneuver.

主要终点是从基线到第28周通过Valsalva动作诱发的左心室流出道压力梯度的变化。

Results

A total of 44 patients underwent randomization; 23 patients (8 [35%] of whom were female) were assigned to mavacamten group, and 21 (5 [24%] of whom were female) were assigned to the placebo group.

共有44名患者进行了随机分组；其中23名患者（8名女性，占35%）被分配到mavacamten组，另外21名患者（5名女性，占24%）被分配到安慰剂组。

The mean (±SD) age of the patients was 14.7±1.7 years in the mavacamten group and 14.6±1.7 years in the placebo group, and the mean Valsalva left ventricular outflow tract gradient at baseline was similar in the two groups (78.4±34.1 mm Hg and 80.8±47.4 mm Hg, respectively).

患者平均年龄在马瓦卡门组为14.7±1.7岁，在安慰剂组为14.6±1.7岁。两组基线时的平均瓦尔萨尔瓦左心室流出道梯度相似（分别为78.4±34.1毫米汞柱和80.8±47.4毫米汞柱）。

At week 28, the least-squares mean change in the Valsalva left ventricular outflow tract gradient was -48.5 mm Hg in the mavacamten group and -0.5 mm Hg in the placebo group (difference, -48.0 mm Hg; 95% confidence interval, -67.7 to -28.3; P<0.001).

在第28周时，马瓦卡门组的瓦尔萨尔瓦左心室流出道梯度的最小二乘平均变化为-48.5毫米汞柱，而安慰剂组为-0.5毫米汞柱（差异，-48.0毫米汞柱；95%置信区间，-67.7至-28.3；P<0.001）。

The incidenceof adverse events was similar in the two groups.

两组中不良事件的发生率相似。

Two patients in each group had serious adverse events; in the mavacamten group, 1 patient had two episodes of syncope, and another had an inappropriate shock delivered by an implantable cardioverter-defibrillator; in the placebo group, 1 patient had chest pain, and another had depression with suicidal ideation.

每组各有两名患者出现严重不良事件；在mavacamten组中，1名患者出现两次晕厥，另1名患者植入的心脏复律除颤器不适当放电；在安慰剂组中，1名患者出现胸痛，另1名患者出现伴有自杀意念的抑郁。

No patient had a reduction in the left ventricular ejection fraction to less than 50%.

在研究中，没有患者的左心室射血分数降低到50%以下。

No deaths occurred during the trial.

在试验期间没有发生任何死亡事件。

Conclusions

Among adolescent patients with obstructive hypertrophic cardiomyopathy, the reduction in left ventricular outflow tract obstruction was significantly greater with mavacamten than with placebo over a 28-week period.

在患有梗阻性肥厚型心肌病的青少年患者中，与安慰剂相比，mavacamten在28周的时间内显著更大程度地减少了左心室流出道梗阻。

(Funded by Bristol Myers Squibb; SCOUT-HCM ClinicalTrials.gov number, NCT06253221.).

(该研究由百时美施贵宝公司资助；SCOUT-HCM的ClinicalTrials.gov编号为NCT06253221。)