Objectives

This study sought to evaluate the efficacy and safety of sacubitril/valsartan according to dose level achieved in the PIONEER-HF (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode) trial.

Background

In patients hospitalized for acute decompensated heart failure (ADHF), in-hospital initiation and continuation of sacubitril/valsartan as compared with enalapril is well tolerated, achieves a greater reduction in N-terminal pro–B-type natriuretic peptide (NT-proBNP), and reduces the risk of cardiovascular death or rehospitalization for HF through 8 weeks. However, not all patients achieve the target dose of sacubitril/valsartan, and its efficacy and safety in such patients are of interest.

Methods

PIONEER-HF was a randomized, double-blind, active-controlled trial of sacubitril/valsartan versus enalapril in 881 patients stabilized during hospitalization for ADHF. Blinded study medication was administered for 8 weeks, with initial dosing selected based on the systolic blood pressure at randomization and titrated toward a target of sacubitril/valsartan 97/103 mg twice daily, or enalapril 10 mg twice daily, with an algorithm based on systolic blood pressure and the investigator’s assessment of tolerability.

Results

At 4 weeks, 199 (55%) patients allocated to sacubitril/valsartan and 211 (60%) patients allocated to enalapril were dispensed the target dose. Baseline characteristics were similar in the 2 treatment groups within each dose level. There was no heterogeneity across dose levels in the effect of sacubitril/valsartan on the reduction in NT-proBNP (p_interaction = 0.69), the reduction in cardiovascular death or rehospitalization for heart failure (p_interaction = 0.42), or the pre-specified adverse events of special interest through 8 weeks.

Conclusions

In hemodynamically stabilized patients with ADHF, the efficacy and safety of sacubitril/valsartan are generally consistent across dose levels. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890)

中文翻译：

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PIONEER-HF 试验中达到的剂量水平的沙库巴曲/缬沙坦的疗效和安全性。

目标

本研究旨在根据 PIONEER-HF（沙库巴曲/缬沙坦与依那普利对急性心力衰竭发作稳定的患者中 NT-proBNP 影响的比较）试验中达到的剂量水平评估沙库巴曲/缬沙坦的疗效和安全性。

背景

在因急性失代偿性心力衰竭 (ADHF) 住院的患者中，与依那普利相比，院内开始和继续使用沙库巴曲/缬沙坦具有良好的耐受性，可实现 N 端 B 型利钠肽原 (NT-proBNP) 更大程度的降低，并通过 8 周降低心血管死亡或 HF 再住院的风险。然而，并非所有患者都能达到沙库巴曲/缬沙坦的目标剂量，其在此类患者中的有效性和安全性值得关注。

方法

PIONEER-HF 是一项在 881 名因 ADHF 住院期间病情稳定的患者中进行的沙库巴曲/缬沙坦与依那普利的随机、双盲、活性对照试验。盲法研究药物给药 8 周，根据随机分组时的收缩压选择初始剂量，并朝着目标沙库巴曲/缬沙坦 97/103 mg 每天两次或依那普利 10 mg 每天两次，使用基于收缩压的算法血压和研究者对耐受性的评估。

结果

在第 4 周时，分配给沙库巴曲/缬沙坦的 199 名患者（55%）和分配给依那普利的 211 名（60%）患者分配了目标剂量。在每个剂量水平内，2 个治疗组的基线特征相似。沙库巴曲/缬沙坦对 NT-proBNP 降低（p_交互作用 = 0.69）、心血管死亡或心力衰竭再住院减少（p_交互作用 = 0.42）或预先指定的影响在剂量水平之间没有异质性8 周内特别关注的不良事件。

结论

在血液动力学稳定的 ADHF 患者中，沙库巴曲/缬沙坦的疗效和安全性在不同剂量水平上通常是一致的。（沙库巴曲/缬沙坦与依那普利对急性心力衰竭稳定患者 NT-proBNP 影响的比较 [PIONEER-HF]；NCT02554890）