Valsartan in early-stage hypertrophic cardiomyopathy: a randomized phase 2 trial.
Valsartan in early-stage hypertrophic cardiomyopathy: a randomized phase 2 trial.
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DOI：
10.1038/s41591-021-01505-4
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发表时间：
2021-10
期刊：
影响因子：
82.9
通讯作者：
Braunwald E
中科院分区：
文献类型：
--
作者：
Ho CY;Day SM;Axelsson A;Russell MW;Zahka K;Lever HM;Pereira AC;Colan SD;Margossian R;Murphy AM;Canter C;Bach RG;Wheeler MT;Rossano JW;Owens AT;Bundgaard H;Benson L;Mestroni L;Taylor MRG;Patel AR;Wilmot I;Thrush P;Vargas JD;Soslow JH;Becker JR;Seidman CE;Lakdawala NK;Cirino AL;VANISH Investigators;Burns KM;McMurray JJV;MacRae CA;Solomon SD;Orav EJ;Braunwald E
肥厚型心肌病（HCM）通常由肌节基因的致病性变异引起，并且以左心室（LV）肥大、心肌纤维化以及心力衰竭和心律失常的风险增加为特征。目前尚无改变疾病进展的治疗方法。在这项研究中，我们进行了一项多中心、双盲、安慰剂对照的2期临床试验，以评估血管紧张素II受体阻滞剂缬沙坦在减轻早期HCM疾病进展方面的安全性和有效性。总共有178名患有早期肌节性HCM的参与者被随机（1：1）接受缬沙坦（成人每日320 mg;儿童每日80-160 mg）或安慰剂治疗2年（NCT 01912534）。从基线到第2年，左心室壁厚度、质量和体积、左心房容积、组织多普勒舒张期和收缩期速度以及高敏肌钙蛋白T和N末端B型利钠蛋白原的血清水平的标准化变化被整合到一个单一的复合z评分中作为主要结局。与安慰剂（n = 90）相比，缬沙坦（n = 88）改善了心脏结构和功能，这反映在复合z评分增加（组间差异+0.231，95%置信区间（+0.098，+0.364）; P = 0.001），符合研究的主要终点。治疗耐受性良好。这些结果表明，使用易于获得且安全的药物来减缓早期肌节HCM疾病进展的关键机会。
Hypertrophic cardiomyopathy (HCM) is often caused by pathogenic variants in sarcomeric genes and characterized by left ventricular (LV) hypertrophy, myocardial fibrosis and increased risk of heart failure and arrhythmias. There are no existing therapies to modify disease progression. In this study, we conducted a multi-center, double-blind, placebo-controlled phase 2 clinical trial to assess the safety and efficacy of the angiotensin II receptor blocker valsartan in attenuating disease evolution in early HCM. In total, 178 participants with early-stage sarcomeric HCM were randomized (1:1) to receive valsartan (320 mg daily in adults; 80–160 mg daily in children) or placebo for 2 years (NCT01912534). Standardized changes from baseline to year 2 in LV wall thickness, mass and volumes; left atrial volume; tissue Doppler diastolic and systolic velocities; and serum levels of high-sensitivity troponin T and N-terminal pro-B-type natriuretic protein were integrated into a single composite z-score as the primary outcome. Valsartan (n = 88) improved cardiac structure and function compared to placebo (n = 90), as reflected by an increase in the composite z-score (between-group difference +0.231, 95% confidence interval (+0.098, +0.364); P = 0.001), which met the primary endpoint of the study. Treatment was well-tolerated. These results indicate a key opportunity to attenuate disease progression in early-stage sarcomeric HCM with an accessible and safe medication.
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