Division of Cardiology, Duke University and Duke Clinical Research Institute, Durham NC, USA.
Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
J Card Fail. 2024 Jun;30(6):755-763. doi: 10.1016/j.cardfail.2023.11.021. Epub 2024 Jan 11.
Omecamtiv mecarbil improves outcomes in patients with heart failure and reduced ejection fraction (HFrEF). We examined the relationship between baseline troponin levels, change in troponin levels over time and the treatment effect of omecamtiv mecarbil in patients enrolled in the Global Approach to Lowering Adverse Cardiac Outcomes through Improving Contractility in Heart Failure (GALACTIC-HF) trial (NCT02929329).
GALACTIC-HF was a double-blind, placebo-controlled trial that randomized 8256 patients with symptomatic HFrEF to omecamtiv mecarbil or placebo. High-sensitivity troponin I (cTnI) was measured serially at a core laboratory. We analyzed the relationship between both baseline cTnI and change in cTnI concentrations with clinical outcomes and the treatment effect of omecamtiv mecarbil.
Higher baseline cTnI concentrations were associated with a risk of adverse outcomes (hazard ratio for the primary endpoint of time to first HF event or CV death = 1.30; 95% CI 1.28, 1.33; P < 0.001 per doubling of baseline cTnI). Although the incidence of safety outcomes was higher in patients with higher baseline cTnI, there was no difference between treatment groups. Treatment with omecamtiv mecarbil led to a modest increase in cTnI that was related to plasma concentrations of omecamtiv mecarbil, and it peaked at 6 weeks. An increase in troponin from baseline to week 6 was associated with an increased risk of the primary endpoint (P < 0.001), which was similar, regardless of treatment assignment (P value for interaction = 0.2).
In a cohort of patients with HFrEF, baseline cTnI concentrations were strongly associated with adverse clinical outcomes. Although cTnI concentrations were higher in patients treated with omecamtiv mecarbil, we did not find a differential effect of omecamtiv mecarbil on either safety or efficacy based on baseline cTnI status or change in cTnI.
Omecamtiv mecarbil 可改善射血分数降低的心力衰竭（HFrEF）患者的结局。我们研究了基线肌钙蛋白水平、随时间变化的肌钙蛋白水平变化与在 Global Approach to Lowering Adverse Cardiac Outcomes through Improving Contractility in Heart Failure（GALACTIC-HF）试验（NCT02929329）中入组的患者接受 Omecamtiv mecarbil 治疗效果之间的关系。
GALACTIC-HF 是一项双盲、安慰剂对照试验，将 8256 例有症状的 HFrEF 患者随机分为 Omecamtiv mecarbil 或安慰剂组。在核心实验室连续测量高敏肌钙蛋白 I（cTnI）。我们分析了基线 cTnI 和 cTnI 浓度变化与临床结局以及 Omecamtiv mecarbil 治疗效果之间的关系。
基线 cTnI 浓度较高与不良结局风险相关（主要终点为首次心力衰竭事件或心血管死亡的时间的风险比 = 1.30；95%CI 1.28，1.33；每增加一倍基线 cTnI，P < 0.001）。虽然基线 cTnI 较高的患者发生安全性结局的发生率较高，但治疗组之间无差异。接受 Omecamtiv mecarbil 治疗可导致 cTnI 适度升高，且与 Omecamtiv mecarbil 的血浆浓度相关，其峰值出现在 6 周时。与基线相比，第 6 周时肌钙蛋白的升高与主要终点的风险增加相关（P < 0.001），无论治疗分配如何，这种相关性均相似（交互作用 P 值 = 0.2）。
在 HFrEF 患者队列中，基线 cTnI 浓度与不良临床结局密切相关。尽管接受 Omecamtiv mecarbil 治疗的患者 cTnI 浓度较高，但我们没有发现 Omecamtiv mecarbil 对基于基线 cTnI 状态或 cTnI 变化的安全性或疗效有差异。
