在GALACTIC-HF(通过改善心力衰竭的收缩力来降低不良心脏结果的全球方法)中(n=8,256),心肌肌球蛋白激活剂,omecamtivmecarbil,在射血分数(EF)降低(≤35%)的心力衰竭患者中,首次心力衰竭事件或心血管死亡的主要复合终点(PCE)显著降低.
本研究的目的是评估基线EF对omecamtivmecarbil治疗效果的影响。
根据EF将omecamtivmecarbil治疗的患者的结果与安慰剂进行比较。
安慰剂组的PCE风险在最低EF(≤22%)的四分位数比最高EF(≥33%)的四分位数高出近1.8倍。在预先指定的子组中,EF是omecamtivmecarbil对PCE的治疗效果最强的调节剂(相互作用为连续变量,p=0.004)。随着基线EF的降低,接受omecamtivmecarbil的患者的相对和绝对治疗效果逐渐增强。基线EF≤22%(n=2,246;风险比:0.83;95%置信区间:0.73至0.95)的患者与EF≥33%(n=1,750;风险比:0.99;95%置信区间:0.84至1.16;通过四分位数作为EF的相互作用,p=0.013)。PCE的绝对降低随着EF的降低而增加(EF≤22%;绝对风险降低,每100个患者年发生7.4个事件;3年需要治疗的数量=11.8),与最高EF四分位数没有减少相比。
在EF降低的心力衰竭患者中,随着基线EF的降低,omecamtivmecarbil产生了更大的治疗益处。这些发现与药物选择性改善收缩功能的机制一致,并为改善一组风险最大的患者的预后提供了重要的机会。(OmecamtivMecarbil/AMG423治疗射血分数降低的慢性心力衰竭的注册研究[GALACTIC-HF];NCT02929329)。
In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure) (n = 8,256), the cardiac myosin activator, omecamtiv mecarbil, significantly reduced the primary composite endpoint (PCE) of time-to-first heart failure event or cardiovascular death in patients with heart failure and reduced ejection fraction (EF) (≤35%).
The purpose of this study was to evaluate the influence of baseline EF on the therapeutic effect of omecamtiv mecarbil.
Outcomes in patients treated with omecamtiv mecarbil were compared with placebo according to EF.
The risk of the PCE in the placebo group was nearly 1.8-fold greater in the lowest EF (≤22%) compared with the highest EF (≥33%) quartile. Amongst the pre-specified subgroups, EF was the strongest modifier of the treatment effect of omecamtiv mecarbil on the PCE (interaction as continuous variable, p = 0.004). Patients receiving omecamtiv mecarbil had a progressively greater relative and absolute treatment effect as baseline EF decreased, with a 17% relative risk reduction for the PCE in patients with baseline EF ≤22% (n = 2,246; hazard ratio: 0.83; 95% confidence interval: 0.73 to 0.95) compared with patients with EF ≥33% (n = 1,750; hazard ratio: 0.99; 95% confidence interval: 0.84 to 1.16; interaction as EF by quartiles, p = 0.013). The absolute reduction in the PCE increased with decreasing EF (EF ≤22%; absolute risk reduction, 7.4 events per 100 patient-years; number needed to treat for 3 years = 11.8), compared with no reduction in the highest EF quartile.
In heart failure patients with reduced EF, omecamtiv mecarbil produced greater therapeutic benefit as baseline EF decreased. These findings are consistent with the drug\'s mechanism of selectively improving systolic function and presents an important opportunity to improve the outcomes in a group of patients at greatest risk. (Registrational Study With Omecamtiv Mecarbil/AMG 423 to Treat Chronic Heart Failure With Reduced Ejection Fraction [GALACTIC-HF]; NCT02929329).