Abstract：
Septal reduction therapy (SRT) in patients with intractable symptoms from obstructive hypertrophic cardiomyopathy (oHCM) is associated with variable morbidity and mortality. The VALOR-HCM trial (A Study to Evaluate Mavacamten in Adults with Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) examined the effect of mavacamten on the need for SRT through week 32 in oHCM.
A double-blind randomized placebo-controlled multicenter trial at 19 US sites included patients with oHCM on maximal tolerated medical therapy referred for SRT with left ventricular outflow tract gradient ≥50 mm Hg at rest or provocation (enrollment, July 2020-October 2021). The group initially randomized to mavacamten continued the drug for 32 weeks, and the placebo group crossed over to dose-blinded mavacamten from week 16 to week 32. Dose titrations were based on investigator-blinded echocardiographic assessment of left ventricular outflow tract gradient and left ventricular ejection fraction. The principal end point was the proportion of patients proceeding with SRT or remaining guideline eligible at 32 weeks in both treatment groups.
From the 112 randomized patients with oHCM, 108 (mean age, 60.3 years; 50% men; 94% in New York Heart Association class III/IV) qualified for week 32 evaluation (56 in the original mavacamten group and 52 in the placebo cross-over group). After 32 weeks, 6 of 56 patients (10.7%) in the original mavacamten group and 7 of 52 patients (13.5%) in the placebo cross-over group met SRT guideline criteria or elected to undergo SRT. After 32 weeks, a sustained reduction in resting left ventricular outflow tract gradient (-33.0 mm Hg [95% CI, -41.1 to -24.9]) and Valsalva left ventricular outflow tract gradient (-43.0 mm Hg [95% CI, -52.1 to -33.9]) was observed in the original mavacamten group. A similar reduction in resting (-33.7 mm Hg [95% CI, -42.2 to -25.2]) and Valsalva (-52.9 mm Hg [95% CI, -63.2 to -42.6]) gradients was quantified in the cross-over group after 16 weeks of mavacamten. After 32 weeks, improvement by ≥1 New York Heart Association class was observed in 48 of 53 patients (90.6%) in the original mavacamten group and 35 of 50 patients (70%) after 16 weeks in the cross-over group.
In severely symptomatic patients with oHCM, 32 weeks of mavacamten treatment showed sustained reduction in the proportion proceeding to SRT or remaining guideline eligible, with similar effects observed in patients who crossed over from placebo after 16 weeks.
URL: https://www.
gov; Unique identifier: NCT04349072.
A double-blind randomized placebo-controlled multicenter trial at 19 US sites included patients with oHCM on maximal tolerated medical therapy referred for SRT with left ventricular outflow tract gradient ≥50 mm Hg at rest or provocation (enrollment, July 2020-October 2021). The group initially randomized to mavacamten continued the drug for 32 weeks, and the placebo group crossed over to dose-blinded mavacamten from week 16 to week 32. Dose titrations were based on investigator-blinded echocardiographic assessment of left ventricular outflow tract gradient and left ventricular ejection fraction. The principal end point was the proportion of patients proceeding with SRT or remaining guideline eligible at 32 weeks in both treatment groups.
From the 112 randomized patients with oHCM, 108 (mean age, 60.3 years; 50% men; 94% in New York Heart Association class III/IV) qualified for week 32 evaluation (56 in the original mavacamten group and 52 in the placebo cross-over group). After 32 weeks, 6 of 56 patients (10.7%) in the original mavacamten group and 7 of 52 patients (13.5%) in the placebo cross-over group met SRT guideline criteria or elected to undergo SRT. After 32 weeks, a sustained reduction in resting left ventricular outflow tract gradient (-33.0 mm Hg [95% CI, -41.1 to -24.9]) and Valsalva left ventricular outflow tract gradient (-43.0 mm Hg [95% CI, -52.1 to -33.9]) was observed in the original mavacamten group. A similar reduction in resting (-33.7 mm Hg [95% CI, -42.2 to -25.2]) and Valsalva (-52.9 mm Hg [95% CI, -63.2 to -42.6]) gradients was quantified in the cross-over group after 16 weeks of mavacamten. After 32 weeks, improvement by ≥1 New York Heart Association class was observed in 48 of 53 patients (90.6%) in the original mavacamten group and 35 of 50 patients (70%) after 16 weeks in the cross-over group.
In severely symptomatic patients with oHCM, 32 weeks of mavacamten treatment showed sustained reduction in the proportion proceeding to SRT or remaining guideline eligible, with similar effects observed in patients who crossed over from placebo after 16 weeks.
URL: https://www.
gov; Unique identifier: NCT04349072.
摘要：
背景：在梗阻性肥厚型心肌病（oHCM）有顽固性症状的患者中，中隔减少治疗（SRT）与不同的发病率和死亡率相关。VALOR-HCM试验检查了mavacten对oHCM中第32周SRT需求的影响。
方法：一项在美国19个地点进行的双盲随机安慰剂对照多中心试验，包括接受SRT的最大耐受药物治疗的oHCM患者，静息或激发时左心室流出道（LVOT）梯度≥50mmHg（202010/2021年7月登记）。最初随机分配给mavacampen的组继续药物32周，安慰剂组从第16周到第32周交叉到剂量盲化的mavacampen。剂量滴定基于LVOT梯度和LV射血分数的研究者盲超声心动图评估。主要终点是两个治疗组在32周时接受SRT或仍符合指南的患者比例。
结果：从112名随机oHCM患者中，108(平均年龄60.3岁，50％的男性和94％的纽约心脏协会[NYHA]III/IV级）符合第32周评估的资格（原始mavacampen中的56和安慰剂交叉组中的52）。32周后,原始mavacampen中的6/56（10.7％）患者和安慰剂交叉组中的7/52（13.5％）患者符合SRT指南标准或选择接受SRT。32周后,静息LVOT梯度（-33.0mmHg95％置信区间[CI]-41.1至-24.9）和ValsalvaLVOT梯度（-43.0mmHg，在原始mavacamten组中观察到95％CI-52.1至-33.9）。类似的静息减少（-33.7mmHg，95%CI-42.2至-25.2）和Valsalva梯度（-52.9mmHg，在mavacamten治疗16周后，交叉组量化了95%CI-63.2至-42.6）。32周后,交叉组16周后，原始mavacampen的48/53（90.6％）和35/50（70％）的NYHA等级改善≥1。
结论：在有严重症状的oHCM患者中，32周的mavacamten治疗显示，SRT或仍符合指南的比例持续降低，在16周后从安慰剂交叉的患者中观察到类似的效果。
背景：URL：Clinicaltrials.gov唯一标识符：NCT04349072。
方法：一项在美国19个地点进行的双盲随机安慰剂对照多中心试验，包括接受SRT的最大耐受药物治疗的oHCM患者，静息或激发时左心室流出道（LVOT）梯度≥50mmHg（202010/2021年7月登记）。最初随机分配给mavacampen的组继续药物32周，安慰剂组从第16周到第32周交叉到剂量盲化的mavacampen。剂量滴定基于LVOT梯度和LV射血分数的研究者盲超声心动图评估。主要终点是两个治疗组在32周时接受SRT或仍符合指南的患者比例。
结果：从112名随机oHCM患者中，108(平均年龄60.3岁，50％的男性和94％的纽约心脏协会[NYHA]III/IV级）符合第32周评估的资格（原始mavacampen中的56和安慰剂交叉组中的52）。32周后,原始mavacampen中的6/56（10.7％）患者和安慰剂交叉组中的7/52（13.5％）患者符合SRT指南标准或选择接受SRT。32周后,静息LVOT梯度（-33.0mmHg95％置信区间[CI]-41.1至-24.9）和ValsalvaLVOT梯度（-43.0mmHg，在原始mavacamten组中观察到95％CI-52.1至-33.9）。类似的静息减少（-33.7mmHg，95%CI-42.2至-25.2）和Valsalva梯度（-52.9mmHg，在mavacamten治疗16周后，交叉组量化了95%CI-63.2至-42.6）。32周后,交叉组16周后，原始mavacampen的48/53（90.6％）和35/50（70％）的NYHA等级改善≥1。
结论：在有严重症状的oHCM患者中，32周的mavacamten治疗显示，SRT或仍符合指南的比例持续降低，在16周后从安慰剂交叉的患者中观察到类似的效果。
背景：URL：Clinicaltrials.gov唯一标识符：NCT04349072。
