Section of Cardiology, San Francisco Veterans Affairs Medical Center, School of Medicine, University of California-San Francisco, San Francisco, California.
Estudios Clinicos Latinoamérica, Rosario, Argentina.
JACC Heart Fail. 2020 Apr;8(4):329-340. doi: 10.1016/j.jchf.2019.12.001. Epub 2020 Feb 6.
A central factor in the pathogenesis of heart failure (HF) with reduced ejection fraction is the initial decrease in systolic function. Prior attempts at increasing cardiac contractility with oral drugs have uniformly resulted in signals of increased mortality at pharmacologically effective doses. Omecamtiv mecarbil is a novel, selective cardiac myosin activator that has been shown to improve cardiac function and to decrease ventricular volumes, heart rate, and N-terminal pro-B-type natriuretic peptide in patients with chronic HF. The GALACTIC-HF (Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure) trial tests the hypotheses that omecamtiv mecarbil can safely improve symptoms, prevent clinical HF events, and delay CV death in patients with chronic HF. The GALACTIC-HF trial is an international, multicenter, randomized, double-blind, placebo-controlled, event-driven cardiovascular outcomes trial. More than 8,000 patients with chronic symptomatic (New York Heart Association functional class II to IV) HF, left ventricular ejection fraction ≤35%, elevated natriuretic peptides, and either current hospitalization for HF or history of hospitalization or emergency department visit for HF within a year of screening will be randomized to either oral placebo or omecamtiv mecarbil employing a pharmacokinetic-guided dose titration strategy using doses of 25, 37.5, or 50 mg twice daily. The primary efficacy outcome is the time to cardiovascular death or first HF event. The study has 90% power to assess a final hazard ratio of approximately 0.80 in cardiovascular death, the first secondary outcome. The GALACTIC-HF trial is the first trial examining whether selectively increasing cardiac contractility in patients with HF with reduced ejection fraction will result in improved clinical outcomes. (Registrational Study With Omecamtiv Mecarbil/AMG 423 to Treat Chronic Heart Failure With Reduced Ejection Fraction [GALACTIC-HF]; NCT02929329).
射血分数降低的心力衰竭（HF）发病机制的一个核心因素是收缩功能的最初下降。先前尝试使用口服药物增加心肌收缩力的尝试，在药理有效剂量下均导致死亡率增加的信号。Omecamtiv mecarbil 是一种新型、选择性的心肌肌球蛋白激活剂，已被证明可改善慢性 HF 患者的心脏功能并降低心室容积、心率和 N 末端 pro-B 型利钠肽。GALACTIC-HF（通过改善心力衰竭中的收缩力降低不良心脏结局的全球方法）试验检验了以下假设：omecamtiv mecarbil 可以安全地改善症状、预防临床 HF 事件并延迟慢性 HF 患者的心血管死亡。GALACTIC-HF 试验是一项国际性、多中心、随机、双盲、安慰剂对照、事件驱动的心血管结局试验。超过 8000 名患有慢性有症状（纽约心脏协会功能分级 II 至 IV 级）HF、左心室射血分数≤35%、升高的利钠肽、并且在筛选后的一年内有 HF 住院或 HF 住院或急诊就诊史的患者将被随机分配接受口服安慰剂或 omecamtiv mecarbil 治疗，采用基于药代动力学的剂量滴定策略，剂量为 25、37.5 或 50mg，每日两次。主要疗效终点是心血管死亡或首次 HF 事件的时间。该研究有 90%的效能评估心血管死亡的最终危险比约为 0.80，这是第二个次要终点。GALACTIC-HF 试验是首个评估选择性增加射血分数降低的心力衰竭患者心肌收缩力是否会改善临床结局的试验。（用 Omecamtiv Mecarbil/AMG 423 治疗射血分数降低的慢性心力衰竭的注册研究[GALACTIC-HF]；NCT02929329）。
