Davis Bryton J, Volk Hailey, Nguyen Olives, Kamna Daniel, Chen Hongya, Barriales-Villa Roberto, Garcia-Pavia Pablo, Olivotto Iacopo, Owens Anjali T, Coats Caroline J, Abraham Theodore P, Solomon Scott D, Maron Martin S, Masri Ahmad
Oregon Health & Science University Portland OR USA.
Complexo Hospitalario Universitario A Coruña, INIBIC, CIBERCV Coruña Spain.
J Am Heart Assoc. 2025 Mar 18;14(6):e038758. doi: 10.1161/JAHA.124.038758. Epub 2025 Mar 7.
Cardiac myosin inhibitors were recently developed to address the underlying pathophysiology of hypertrophic cardiomyopathy and to improve symptoms and quality of life. In this review, we evaluated the pharmacologic profile and clinical outcomes for mavacamten and aficamten, 2 cardiac myosin inhibitors investigated in symptomatic hypertrophic cardiomyopathy.
Using a systematic search, 10 clinical trials with safety and efficacy data for either drug in obstructive hypertrophic cardiomyopathy (oHCM) and nonobstructive hypertrophic cardiomyopathy were included. Additionally, we included data from regulatory agencies. Both drugs demonstrated substantial benefit in reducing left ventricular outflow tract obstruction (Valsalva left ventricular outflow tract gradients improved by -45 mm Hg or better), symptom burden (placebo-corrected New York Heart Association class improvement ≥1 of at least 30%), and cardiac biomarkers (geometric mean ratio of 0.2 for N-terminal pro-B-type natriuretic peptide) while improving exercise parameters (improved placebo-corrected peak oxygen consumption of at least 1.4 to 1.8 mL/kg per minute) in patients with oHCM. Both drugs were generally well-tolerated, although patients on mavacamten had higher rates of treatment interruption (partly protocol-driven, 8.7% versus 0.5%, respectively, in oHCM) due to left ventricular ejection fraction reduction, atrial fibrillation (11.5 versus 4.1 per 100 patient-years, respectively, in oHCM), and heart failure (1.7 versus 0.0 per 100 patient-years, respectively, in oHCM) compared with aficamten. These comparisons are limited by a shorter exposure duration to aficamten, and longer follow-up is needed. The data in nonobstructive hypertrophic cardiomyopathy are derived from phase II trials, with phase III trials ongoing.
Mavacamten and aficamten represent effective medications for the treatment of symptomatic oHCM.
心脏肌球蛋白抑制剂最近被开发出来，以解决肥厚型心肌病的潜在病理生理学问题，并改善症状和生活质量。在本综述中，我们评估了mavacamten和aficamten这两种用于有症状肥厚型心肌病研究的心脏肌球蛋白抑制剂的药理学特征和临床结果。
通过系统检索，纳入了10项关于梗阻性肥厚型心肌病（oHCM）和非梗阻性肥厚型心肌病中任一药物的安全性和有效性数据的临床试验。此外，我们还纳入了监管机构的数据。两种药物在减少左心室流出道梗阻（瓦尔萨尔瓦动作时左心室流出道压力阶差改善-45 mmHg或更好）、症状负担（经安慰剂校正后纽约心脏协会心功能分级改善≥1级，至少30%）和心脏生物标志物（N末端B型利钠肽原几何平均比值为0.2）方面均显示出显著益处，同时改善了oHCM患者的运动参数（经安慰剂校正后峰值耗氧量至少提高1.4至1.8 mL/kg每分钟）。两种药物总体耐受性良好，尽管与aficamten相比，服用mavacamten的患者因左心室射血分数降低、心房颤动（oHCM中分别为每100患者年11.5例和4.1例）和心力衰竭（oHCM中分别为每100患者年1.7例和0.0例）导致治疗中断的发生率更高（部分由方案驱动，oHCM中分别为8.7%和0.5%）。这些比较因aficamten的暴露持续时间较短而受到限制，需要更长时间的随访。非梗阻性肥厚型心肌病的数据来自II期试验，III期试验正在进行中。
Mavacamten和aficamten是治疗有症状oHCM的有效药物。
