射血分数、生物标志物以及维立西呱对 VICTORIA 研究中 EF 各亚组患者结局的影响和作用。
Ejection Fraction, Biomarkers, and Outcomes and Impact of Vericiguat on Outcomes Across EF in VICTORIA.
机构信息
Baylor University Medical Center, Dallas, Texas, USA; Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada.
出版信息
JACC Heart Fail. 2023 May;11(5):583-592. doi: 10.1016/j.jchf.2022.12.014. Epub 2023 Apr 12.
BACKGROUND
Vericiguat reduced the risk of cardiovascular death (CVD) or hospitalization for heart failure (HF) in patients with worsening HF and reduced left ventricular ejection fraction (LVEF).
OBJECTIVES
The authors assessed the association of LVEF with biomarker levels, risk of outcome, and whether the effect of vericiguat was homogeneous across LVEF in the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure With Reduced Ejection Fraction) trial.
METHODS
Patients were grouped by LVEF tertiles (≤24%, 25%-33%, and >33%). Patient characteristics, clinical outcomes, and efficacy and safety of vericiguat were examined by tertile. Prespecified biomarkers including N-terminal pro-B-type natriuretic peptide, cardiac troponin T, growth differentiation factor 15, interleukin 6, high-sensitivity C-reactive protein, and cystatin C were examined.
RESULTS
The mean LVEF was 29% ± 8% (range: 5%-45%). A pattern of higher N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and interleukin 6 was evident in patients in the lowest LVEF tertile vs the other tertiles. Patients with lower LVEF experienced higher rates of the composite outcome (41.7%, 36.3%, and 33.4% for LVEF ≤24, 25-33, and >33; P < 0.001). There was no significant treatment effect heterogeneity of vericiguat across LVEF groups (adjusted HR from lowest to highest tertiles: 0.79 [95% CI: 0.68-0.94]; 0.95 [95% CI: 0.82-1.11]; 0.94 [95% CI: 0.79-1.11]; P for interaction = 0.222), although the HR was numerically lower in the lowest tertile. There was also no heterogeneity of effect for CVD and HF hospitalization individually (P interaction for CVD = 0.964; HF hospitalization = 0.438). Discontinuation of treatment because of adverse events, symptomatic hypotension, or syncope was consistent across the range of LVEF.
CONCLUSIONS
Patients with lower LVEF had a distinctive biomarker profile and a higher risk for adverse clinical outcomes vs those with a higher LVEF. There was no significant interaction for the benefit of vericiguat across LVEF tertiles, although the largest signal for benefit in both the primary outcome and HF hospitalizations was noted in tertile 1 (LVEF ≤24%). (Vericiguat Global Study in Subjects with Heart Failure With Reduced Ejection Fraction [VICTORIA]; NCT02861534).
背景
维立西呱降低了射血分数降低的心力衰竭（HF）恶化患者的心血管死亡（CVD）或 HF 住院风险。
目的
作者评估了左心室射血分数（LVEF）与生物标志物水平、结局风险的相关性，以及维立西呱在 VICTORIA（维立西呱治疗射血分数降低的心力衰竭患者的全球研究）试验中的疗效是否在 LVEF 范围内具有均一性。
方法
根据 LVEF 三分位（≤24%、25%-33%和＞33%）对患者进行分组。通过三分位检验患者特征、临床结局以及维立西呱的疗效和安全性。还检验了预先指定的生物标志物，包括 N 末端 B 型利钠肽原、心脏肌钙蛋白 T、生长分化因子 15、白细胞介素 6、高敏 C 反应蛋白和胱抑素 C。
结果
LVEF 的平均值为 29%±8%（范围：5%-45%）。与其他三分位相比，LVEF 最低三分位的患者 N 末端 B 型利钠肽原、高敏 C 反应蛋白和白细胞介素 6 水平更高。LVEF 较低的患者复合结局发生率更高（LVEF≤24%、25%-33%和＞33%的患者分别为 41.7%、36.3%和 33.4%；P＜0.001）。维立西呱在 LVEF 组之间的治疗效果无显著的异质性（从最低到最高三分位的调整 HR：0.79[95%CI：0.68-0.94]；0.95[95%CI：0.82-1.11]；0.94[95%CI：0.79-1.11]；P 交互=0.222），尽管在最低三分位的 HR 数值较低。CVD 和 HF 住院的疗效也没有异质性（CVD 的 P 交互=0.964；HF 住院=0.438）。由于不良反应、症状性低血压或晕厥而停止治疗的情况在整个 LVEF 范围内是一致的。
结论
与 LVEF 较高的患者相比，LVEF 较低的患者具有独特的生物标志物特征和更高的不良临床结局风险。尽管在主要结局和 HF 住院方面，第 1 三分位（LVEF≤24%）的获益最大，但维立西呱在 LVEF 三分位之间的获益没有显著的交互作用。（维立西呱治疗射血分数降低的心力衰竭患者的全球研究[VICTORIA]；NCT02861534）。
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