Lahey Hospital and Medical Center, Burlington, Massachusetts, USA.
Oregon Health and Science University, Portland, Oregon, USA.
J Am Coll Cardiol. 2024 Nov 5;84(19):1821-1831. doi: 10.1016/j.jacc.2024.09.003. Epub 2024 Sep 30.
Aficamten is a cardiac myosin inhibitor that mitigates left ventricular outflow gradients in obstructive hypertrophic cardiomyopathy (oHCM). The clinical efficacy of aficamten across multiple outcome domains in oHCM has not been fully defined.
This responder analysis from the SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM) trial characterizes the clinical impact of aficamten.
Patients who were symptomatic of oHCM were randomized to aficamten (n = 142) or placebo (n = 140) daily for 24 weeks. Outcomes assessed included the proportion of patients with complete hemodynamic response (rest and Valsalva gradient <30 mm Hg and <50 mm Hg, respectively), relief in limiting symptoms (≥1 improvement in NYHA functional class and/or ≥10-point change in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score), enhanced exercise capacity (≥1.5 mL/kg/min change in peak oxygen uptake), and ≥50% reduction in N-terminal pro-B-type natriuretic peptide. Eligibility for septal reduction therapy was also evaluated.
At 24 weeks, patients treated with aficamten vs placebo showed significant improvement in limiting symptoms (71% vs 42%), were more likely to have complete hemodynamic response (68% vs 7%), demonstrated enhanced exercise capacity (47% vs 24%), and showed a decrease ≥50% in N-terminal pro-B-type natriuretic peptide (84% vs 8%) (P ≤ 0.002 for all). An improvement in ≥1 of these outcome measures was achieved in 97% of patients treated with aficamten (vs 59% placebo), including 23% on aficamten who achieved all 4 outcomes compared with none in placebo. Among 32 patients receiving aficamten and 29 patients receiving placebo who were eligible for septal reduction therapy, 28 (88%) from the aficamten group were no longer eligible at 24 weeks compared with 15 (52%) from the placebo group (P = 0.002).
Treatment with aficamten was associated with substantial improvements across a broad range of clinically relevant efficacy measures. These results underscore the wide-ranging potential of aficamten for treatment of patients with symptomatic oHCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults with oHCM [SEQUOIA-HCM]; NCT05186818).
Aficamten 是一种心肌肌球蛋白抑制剂，可减轻梗阻性肥厚型心肌病（oHCM）患者的左心室流出道梯度。在 oHCM 中，aficamten 在多个结局领域的临床疗效尚未完全明确。
本研究来自 SEQUOIA-HCM（评估 Aficamten 与安慰剂治疗有症状的 oHCM 成人的疗效和安全性的 3 期试验），对该试验的应答者分析描述了 aficamten 的临床影响。
患有 oHCM 症状的患者被随机分为 aficamten 组（n=142）或安慰剂组（n=140），每天治疗 24 周。评估的结局包括完全血流动力学应答的患者比例（静息和valsalva 梯度分别<30mmHg 和<50mmHg），限制症状缓解（纽约心脏协会心功能分级至少改善 1 级和/或堪萨斯城心肌病问卷临床综合评分至少改善 10 分），运动能力增强（峰值摄氧量至少增加 1.5mL/kg/min），以及 N 末端 pro-B 型利钠肽降低≥50%。还评估了间隔切开术的入选资格。
24 周时，与安慰剂相比，接受 aficamten 治疗的患者限制症状明显改善（71% vs 42%），更有可能达到完全血流动力学应答（68% vs 7%），运动能力增强（47% vs 24%），以及 N 末端 pro-B 型利钠肽降低≥50%（84% vs 8%）（所有 P 值均≤0.002）。接受 aficamten 治疗的患者中有 97%（32/33）改善了≥1 项上述结局，而安慰剂组为 59%（29/50）（P<0.002）。在 32 名接受 aficamten 和 29 名接受安慰剂且符合间隔切开术入选条件的患者中，24 周时，与安慰剂组的 15 名（52%）患者相比，aficamten 组的 28 名（88%）患者不再符合间隔切开术入选标准（P=0.002）。
aficamten 治疗与广泛的临床相关疗效指标的显著改善相关。这些结果突出了 aficamten 治疗有症状的 oHCM 患者的广泛潜力（评估 Aficamten 与安慰剂治疗有症状的 oHCM 成人的疗效和安全性的 3 期试验[SEQUOIA-HCM]；NCT05186818）。
