背景:2期PIONEER-HCM(2期开放标签试验研究评估Mavacamten在有症状的肥厚型心肌病和左心室流出道梗阻的受试者中)研究表明,Mavacamten改善了左心室流出道梯度,锻炼能力,阻塞性肥厚型心肌病(HCM)患者的症状,但是长期治疗的结果描述得不太好。我们报告了PIONEER-OLE(PIONEER开放标签扩展)研究的中期结果,Mavacamten在有症状的阻塞性HCM患者中的长期研究。
结果:先前完成PIONEER-HCM(n=20)的患者有资格参加PIONEER-OLE。患者接受口服mavacamten,5毫克,每日一次(起始剂量),在第6周进行个体化剂量滴定。评估包括安全的连续监测,超声心动图,堪萨斯城心肌病问卷-总体摘要评分,和血清NT-proBNP(N末端B型利钠肽原)水平。13例患者入组并接受mavacampen(数据截止时的中位研究持续时间,201周)。大多数患者(92.3%)同时接受β受体阻滞剂。治疗引起的不良事件主要为轻度/中度。一名患者的左心室射血分数单独降低至47%,以减少的剂量继续治疗,恢复并保持正常。在第180周,mavacampen与纽约心脏协会从基线的改善有关(II级至I级,n=9;III级至II级,n=1;并且不变,n=2),左心室流出道梯度持续降低(与基线相比的平均[SD]变化:静息,-50[55]mmHg;Valsalva,-70[41]mmHg),和血清NT-proBNP水平(从基线的中位数[四分位数范围]变化:-498[-2184至-76]ng/L),和改善堪萨斯城心肌病问卷-总体汇总评分(从基线的平均[SD]变化:+17[16])。
结论:这项长期分析支持mavacamten在阻塞性HCM中持续3年以上的安全性和有效性。
背景:URL:https://www。clinicaltrials.gov;唯一标识符:NCT03496168。
BACKGROUND: The phase 2 PIONEER-HCM (Phase 2 Open-label Pilot
Study Evaluating Mavacamten in Subjects With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction)
study showed that mavacamten improved left ventricular outflow tract gradients, exercise capacity, and symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM), but the results of longer-term treatment are less well described. We report interim results from the PIONEER-OLE (PIONEER Open-Label Extension)
study, the longest-term
study of mavacamten in patients with symptomatic obstructive HCM.
RESULTS: Patients who previously completed PIONEER-HCM (n=20) were eligible to enroll in PIONEER-OLE. Patients received oral mavacamten, 5 mg once daily (starting dose), with individualized dose titration at week 6. Evaluations included serial monitoring of safety, echocardiography, Kansas City Cardiomyopathy Questionnaire-Overall Summary Score, and serum NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. Thirteen patients enrolled and received mavacamten (median
study duration at data cutoff, 201 weeks). Most patients (92.3%) received β-blockers concomitantly. Treatment-emergent adverse events were predominantly mild/moderate. One patient had an isolated reduction in left ventricular ejection fraction to 47%, which recovered and remained normal with continued treatment at a reduced dose. At week 180, mavacamten was associated with New York Heart Association class improvements from baseline (class II to I, n=9; class III to II, n=1; and unchanged, n=2), sustained reductions in left ventricular outflow tract gradients (mean [SD] change from baseline: resting, -50 [55] mm Hg; Valsalva, -70 [41] mm Hg), and serum NT-proBNP levels (median [interquartile range] change from baseline: -498 [-2184 to -76] ng/L), and improved Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (mean [SD] change from baseline: +17 [16]).
CONCLUSIONS: This long-term analysis supports the continued safety and effectiveness of mavacamten for >3 years in obstructive HCM.
BACKGROUND: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03496168.