Kittipibul Veraprapas, Cyr Derek D, Harrington Josephine, Lala Anuradha, Fudim Marat, Ward Jonathan H, Sarwat Samiha, Solomon Scott D, Hernandez Adrian F, Zieroth Shelley, Starling Randall C, Mentz Robert J
Duke Clinical Research Institute, Durham, NC; Division of Cardiology, Duke University School of Medicine, Durham, NC.
Duke Clinical Research Institute, Durham, NC.
Am Heart J. 2025 Nov;289:105-116. doi: 10.1016/j.ahj.2025.05.004. Epub 2025 May 22.
PARAGLIDE-HF showed significantly greater reduction in NT-proBNP in patients with LVEF>40% and worsening HF with sacubitril/valsartan (sac/val) vs valsartan (val). The impact of structural abnormalities on the effects of sac/val in this context is unknown. This study aimed to evaluate the impact of left ventricular hypertrophy (LVH) and left atrial enlargement (LAE) on sac/val in patients with LVEF>40% and worsening HF.
PARAGLIDE-HF patients were classified into 3 groups according the degree of structural abnormalities using LVH and LAE. The primary endpoint was time-averaged proportional change in NT-proBNP from baseline to Weeks 4 and 8. Secondary endpoints were recurrent cardiovascular composite events (HF hospitalizations, urgent HF visits, cardiovascular death) and adverse events (symptomatic hypotension, hyperkalemia, worsening renal function).
Of 454 (97.4%) patients with LVH and LAE data, 157 (34.5%) had both LVH and LAE, 178 (39.2%) had either LVH or LAE, and 119 (26.2%) had neither LVH nor LAE. Greater reduction in NT-proBNP with sac/val vs val was consistent across groups (P interaction = 0.705). There was no significant interaction between treatment and degree of structural abnormalities for other efficacy endpoints. Patients with both LVH and LAE had significantly higher odds of hyperkalemia with sac/val (OR 2.41, P interaction = 0.024).
Patients with LVEF>40% and recent WHF had greater reduction in NT-proBNP with sac/val vs val, regardless of the degree of structural abnormalities. There was no difference in the effects of sac/val on efficacy endpoints across structural abnormality group. Patients with both LVH and LAE had higher odds for hyperkalemia with sac/val.
PARAGLIDE-HF研究显示，对于左心室射血分数（LVEF）>40%且心力衰竭（HF）症状恶化的患者，与缬沙坦相比，沙库巴曲缬沙坦（沙库/缬）能更显著地降低N末端B型利钠肽原（NT-proBNP）水平。在此背景下，结构异常对沙库/缬疗效的影响尚不清楚。本研究旨在评估左心室肥厚（LVH）和左心房扩大（LAE）对LVEF>40%且HF症状恶化患者使用沙库/缬的影响。
根据LVH和LAE的结构异常程度，将PARAGLIDE-HF研究中的患者分为3组。主要终点是从基线到第4周和第8周NT-proBNP的时间平均比例变化。次要终点是心血管复合事件复发（HF住院、紧急HF就诊、心血管死亡）和不良事件（症状性低血压、高钾血症、肾功能恶化）。
在454例（97.4%）有LVH和LAE数据的患者中，157例（34.5%）同时有LVH和LAE，178例（39.2%）有LVH或LAE，119例（26.2%）既无LVH也无LAE。沙库/缬组NT-proBNP降低幅度大于缬沙坦组，在各亚组中均一致（P交互作用= 0.705）。对于其他疗效终点，治疗与结构异常程度之间无显著交互作用。同时有LVH和LAE的患者使用沙库/缬后发生高钾血症的几率显著更高（比值比2.41，P交互作用= 0.024）。
LVEF>40%且近期发生症状性HF的患者，与缬沙坦相比，使用沙库/缬能更大幅度地降低NT-proBNP，且不受结构异常程度的影响。沙库/缬对各结构异常亚组疗效终点的影响无差异。同时有LVH和LAE的患者使用沙库/缬后发生高钾血症的几率更高。
