Oregon Health & Science University, Portland, Oregon (S.B.H.).
Yale New Haven Hospital, New Haven, Connecticut (D.J.).
Ann Intern Med. 2019 Jun 4;170(11):741-748. doi: 10.7326/M18-3016. Epub 2019 Apr 30.
Mavacamten, an orally administered, small-molecule modulator of cardiac myosin, targets underlying biomechanical abnormalities in obstructive hypertrophic cardiomyopathy (oHCM).
To characterize the effect of mavacamten on left ventricular outflow tract (LVOT) gradient.
Open-label, nonrandomized, phase 2 trial. (ClinicalTrials.gov: NCT02842242).
5 academic centers.
21 symptomatic patients with oHCM.
Patients in cohort A received mavacamten, 10 to 20 mg/d, without background medications. Those in cohort B received mavacamten, 2 to 5 mg/d, with β-blockers allowed.
The primary end point was change in postexercise LVOT gradient at 12 weeks. Secondary end points included changes in peak oxygen consumption (pVO2), resting and Valsalva LVOT gradients, left ventricular ejection fraction (LVEF), and numerical rating scale dyspnea score.
In cohort A, mavacamten reduced mean postexercise LVOT gradient from 103 mm Hg (SD, 50) at baseline to 19 mm Hg (SD, 13) at 12 weeks (mean change, -89.5 mm Hg [95% CI, -138.3 to -40.7 mm Hg]; P = 0.008). Resting LVEF was also reduced (mean change, -15% [CI, -23% to -6%]). Peak VO2 increased by a mean of 3.5 mL/kg/min (CI, 1.2 to 5.9 mL/kg/min). In cohort B, the mean postexercise LVOT gradient decreased from 86 mm Hg (SD, 43) to 64 mm Hg (SD, 26) (mean change, -25.0 mm Hg [CI, -47.1 to -3.0 mm Hg]; P = 0.020), and mean change in resting LVEF was -6% (CI, -10% to -1%). Peak VO2 increased by a mean of 1.7 mL/kg/min (SD, 2.3) (CI, 0.03 to 3.3 mL/kg/min). Dyspnea scores improved in both cohorts. Mavacamten was well tolerated, with mostly mild (80%), moderate (19%), and unrelated (79%) adverse events. The most common adverse events definitely or possibly related to mavacamten were decreased LVEF at higher plasma concentrations and atrial fibrillation.
Small size; open-label design.
Mavacamten can reduce LVOT obstruction and improve exercise capacity and symptoms in patients with oHCM.
MyoKardia.
马卡塞坦是一种口服小分子心肌肌球蛋白调节剂，针对梗阻性肥厚型心肌病（oHCM）的潜在生物力学异常。
描述马卡塞坦对左心室流出道（LVOT）梯度的影响。
开放标签、非随机、2 期试验。（ClinicalTrials.gov：NCT02842242）。
5 个学术中心。
21 名有症状的 oHCM 患者。
A 队列的患者接受马卡塞坦，剂量为 10 至 20mg/d，无背景药物。B 队列的患者接受马卡塞坦，剂量为 2 至 5mg/d，允许使用β受体阻滞剂。
主要终点是 12 周时运动后 LVOT 梯度的变化。次要终点包括峰值氧耗量（pVO2）、静息和valsalva LVOT 梯度、左心室射血分数（LVEF）和数字评分呼吸困难量表的变化。
在 A 队列中，马卡塞坦使平均运动后 LVOT 梯度从基线时的 103mmHg（SD，50）降至 12 周时的 19mmHg（SD，13）（平均变化，-89.5mmHg[95%CI，-138.3 至-40.7mmHg]；P=0.008）。静息 LVEF 也降低（平均变化，-15%[CI，-23%至-6%]）。峰值 VO2 平均增加 3.5mL/kg/min（CI，1.2 至 5.9mL/kg/min）。在 B 队列中，运动后 LVOT 梯度从 86mmHg（SD，43）降至 64mmHg（SD，26）（平均变化，-25.0mmHg[CI，-47.1 至-3.0mmHg]；P=0.020），静息 LVEF 的平均变化为-6%（CI，-10%至-1%）。峰值 VO2 平均增加 1.7mL/kg/min（SD，2.3）（CI，0.03 至 3.3mL/kg/min）。两个队列的呼吸困难评分均有所改善。马卡塞坦耐受性良好，大多数为轻度（80%）、中度（19%）和无关（79%）不良事件。与马卡塞坦绝对或可能相关的最常见不良事件是较高血浆浓度时的 LVEF 降低和心房颤动。
规模小；开放标签设计。
马卡塞坦可降低 oHCM 患者的 LVOT 梗阻，改善运动能力和症状。
MyoKardia。
