Assessment of Omecamtiv Mecarbil for the Treatment of Patients With Severe Heart Failure A Post Hoc Analysis of Data From the GALACTIC-HF Randomized Clinical Trial
Assessment of Omecamtiv Mecarbil for the Treatment of Patients With Severe Heart Failure A Post Hoc Analysis of Data From the GALACTIC-HF Randomized Clinical Trial
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DOI：
10.1001/jamacardio.2021.4027
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发表时间：
2021-10-13
期刊：
影响因子：
24
通讯作者：
Teerlink, John R.
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文献类型：
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作者：
Felker, G. Michael;Solomon, Scott D.;Teerlink, John R.
心力衰竭伴射血分数降低是一种进展性的临床综合征，许多患者的病情会随着时间的推移而恶化，尽管接受了治疗。目的评价参加通过改善心力衰竭收缩能力降低不良心脏结局的全球方法(Galaxy-HF)的患者的有效性和安全性。设计、设置和配对银河-HF研究是一项全球双盲、安慰剂对照的3期随机临床试验，于2017年1月至2020年8月在多个中心进行。共有8232名有症状的心衰患者(定义为纽约心脏协会症状分级II-IV级)和左心室射血分数小于或等于35%的患者被随机分成两组，分别接受奥卡米夫、美卡比利或安慰剂治疗，平均随访时间为21.8个月(范围为15.4-28.6个月)。目前的事后分析评估了与没有严重心力衰竭的患者相比，在被归类为重度心力衰竭的患者中使用奥美卡米治疗的有效性和安全性。重度心力衰竭定义为存在以下所有标准：纽约心脏协会症状分级III至IV级，左心室射血分数小于或等于30%，以及在过去6个月内因心力衰竭住院。干预参与者按1：1的比例随机接受奥美卡比利或安慰剂治疗。主要结果和测量主要终点是首次心力衰竭事件或心血管(CV)死亡的时间。次要终点包括心血管死亡时间、安全性和耐受性。结果在参加银河心衰临床试验的8232名患者中，2258名患者(27.4%；平均年龄64.5[11.6]岁；1781名男性[78.9%])符合指定的重度心力衰竭标准。在这些患者中，1106名患者被随机分到奥米卡米夫组和1152名安慰剂组。接受奥卡米夫-美卡比利治疗的重度心力衰竭患者在主要终点有显著的治疗益处(风险比[HR]，0.80；95%CI，0.71-0.90)，而没有重度心力衰竭的患者没有显著的治疗益处(HR，0.99；95%CI，0.91-1.08；交互作用P=.005)。对于心血管死亡，结果是相似的(有VS无严重心力衰竭患者的HR：0.88[95%CI，0.75-1.03]vs 1.10[95%CI，0.97-1.25]；P=0.03交互作用)。与安慰剂相比，重度心力衰竭患者对奥卡米夫·美卡比利的耐受性良好，血压、肾功能或血钾水平没有明显变化。结论在银河-心力衰竭临床试验数据的事后分析中，奥卡米夫·美卡比利治疗可能在临床上有意义地减少重症心力衰竭患者首次心力衰竭事件或心血管死亡的综合终点。这些数据支持在目前治疗选择有限的患者中使用奥卡米夫美卡比利治疗的潜在作用。(C)2021年美国医学会。版权所有。
IMPORTANCE Heart failure with reduced ejection fraction is a progressive clinical syndrome, and many patients' condition worsen over time despite treatment. Patients with more severe disease are often intolerant of available medical therapies.OBJECTIVE To evaluate the efficacy and safety of omecamtiv mecarbil for the treatment of patients with severe heart failure (HF) enrolled in the Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) randomized clinical trial.DESIGN, SETTING, AND PARTICIPANTSThe GALACTIC-HF study was a global double-blind, placebo-controlled phase 3 randomized clinical trial that was conducted at multiple centers between January 2017 and August 2020. A total of 8232 patients with symptomatic HF (defined as New York Heart Association symptom class II-IV) and left ventricular ejection fraction of 35% or less were randomized to receive omecamtiv mecarbil or placebo and followed up for a median of 21.8 months (range, 15.4-28.6 months). The current post hoc analysis evaluated the efficacy and safety of omecamtiv mecarbil therapy among patients classified as having severe HF compared with patients without severe HF. Severe HF was defined as the presence of all of the following criteria: New York Heart Association symptom class III to IV, left ventricular ejection fraction of 30% or less, and hospitalization for HF within the previous 6 months.INTERVENTIONS Participants were randomized at a 1:1 ratio to receive either omecamtiv mecarbil or placebo.MAIN OUTCOMES AND MEASURES The primary end point was time to first HF event or cardiovascular (CV) death. Secondary end points included time to CV death and safety and tolerability.RESULTS Among 8232 patients enrolled in the GALACTIC-HF clinical trial, 2258 patients (27.4%; mean [SD] age, 64.5 [11.6] years; 1781 men [78.9%]) met the specified criteria for severe HF. Of those, 1106 patients were randomized to the omecamtiv mecarbil group and 1152 to the placebo group. Patients with severe HF who received omecamtiv mecarbil experienced a significant treatment benefit for the primary end point (hazard ratio [HR], 0.80; 95% CI, 0.71-0.90), whereas patients without severe HF had no significant treatment benefit (HR, 0.99; 95% CI, 0.91-1.08; P = .005 for interaction). For CV death, the results were similar (HR for patients with vs without severe HF: 0.88 [95% CI, 0.75-1.03] vs 1.10 [95% CI, 0.97-1.25]; P = .03 for interaction). Omecamtiv mecarbil therapy was well tolerated in patients with severe HF, with no significant changes in blood pressure, kidney function, or potassium level compared with placebo.CONCLUSIONS AND RELEVANCE In this post hoc analysis of data from the GALACTIC-HF clinical trial, omecamtiv mecarbil therapy may have provided a clinically meaningful reduction in the composite end point of time to first HF event or CV death among patients with severe HF. These data support a potential role of omecamtiv mecarbil therapy among patients for whom current treatment options are limited. (C) 2021 American Medical Association. All rights reserved.