OBJECTIVES The authors sought to evaluate the prognostic significance of baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP), whether NT-proBNP modified the treatment response to sacubitril/valsartan, and the treatment effect of sacubitril/valsartan on NT-proBNP overall and in key subgroups. BACKGROUND Sacubitril/valsartan reduces NT-proBNP in heart failure (HF) with both reduced and preserved ejection fraction (EF), but did not significantly reduce total HF hospitalizations and cardiovascular death compared with valsartan in patients with HF with preserved EF (HFpEF). METHODS In the PARAGON-HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) trial, 4,796 patients with HFpEF and elevated NT-proBNP were randomized to sacubitril/valsartan or valsartan. NT-proBNP was measured at screening in all patients and at 5 subsequent times in >2,700 patients: before, between, and after sequential valsartan and sacubitril/valsartan run-in periods, and 16 and 48 weeks post-randomization. RESULTS Median NT-proBNP was 911 pg/ml (interquartile range: 464 to 1,613 pg/ml) at screening. Screening NT-proBNP was strongly associated with the primary endpoint, total HF hospitalizations and cardiovascular death (rate ratio [RR]: 1.68 per log increase in NT-proBNP, 95% confidence interval [CI]: 1.53 to 1.85; p < 0.001). This relationship was stronger in patients with atrial fibrillation (adjusted RR: 2.33 [95% CI: 1.89 to 2.87] vs. 1.58 [95% CI: 1.42 to 1.75] in patients without atrial fibrillation; p interaction <0.001) and weaker in obese patients (adjusted RR: 1.50 [95% CI: 1.31 to 1.71] vs. 1.92 [95% CI: 1.70 to 2.17] in nonobese patients; p interaction <0.001). Screening NT-proBNP did not modify the treatment effect of sacubitril/valsartan compared with valsartan (p interaction = 0.96). Sacubitril/valsartan reduced NT-proBNP by 19% (95% CI: 14% to 23%; p < 0.001) compared with valsartan 16 weeks post-randomization, with similar reductions in men (20%) and women (18%), and in patients with left ventricular EF ≤57% (20%) and >57% (18%). Decreases in NT-proBNP predicted lower subsequent risk of the primary endpoint. CONCLUSIONS Baseline NT-proBNP predicted HF events but did not modify the sacubitril/valsartan treatment effect in patients with HFpEF. Sacubitril/valsartan reduced NT-proBNP consistently in men and women, and in patients with lower or higher EF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).

中文翻译：

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沙库巴曲/缬沙坦对射血分数保留的心力衰竭中 N 端 B 型利尿钠肽的影响。

目的 作者试图评估基线 N 末端 B 型利钠肽原 (NT-proBNP) 的预后意义、NT-proBNP 是否改变对沙库巴曲/缬沙坦的治疗反应，以及沙库巴曲/缬沙坦对 NT 的治疗效果-proBNP 总体和关键亚组。背景沙库巴曲/缬沙坦可降低射血分数（EF）降低和保留的心力衰竭（HF）患者的 NT-proBNP，但与 EF 保留的心力衰竭（HFpEF）患者相比，沙库巴曲/缬沙坦并未显着减少 HF 住院总人数和心血管死亡。方法 在 PARAGON-HF（LCZ696 与缬沙坦相比，对射血分数保留的心力衰竭患者的发病率和死亡率的疗效和安全性）试验中，4,796 名 HFpEF 和 NT-proBNP 升高的患者被随机分配至沙库巴曲/缬沙坦或缬沙坦组。在筛选时对所有患者进行了 NT-proBNP 测量，并对超过 2,700 名患者进行了后续 5 次测量：序贯缬沙坦和沙库巴曲/缬沙坦磨合期之前、之间和之后，以及随机分组后 16 周和 48 周。结果 筛选时 NT-proBNP 中位数为 911 pg/ml（四分位数范围：464 至 1,613 pg/ml）。NT-proBNP 筛查与主要终点、心力衰竭住院总数和心血管死亡密切相关（比率 [RR]：NT-proBNP 每对数增加 1.68，95% 置信区间 [CI]：1.53 至 1.85；p < 0.001） 。这种关系在心房颤动患者中更强（调整后 RR：2.33 [95% CI：1.89 至 2.87] 对比无心房颤动患者中的 1.58 [95% CI：1.42 至 1.75]；p 相互作用 <0.001），而在肥胖患者中则较弱患者（调整后的 RR：1.50 [95% CI：1.31 至 1.71] 对比非肥胖患者的 1.92 [95% CI：1.70 至 2.17]；p 交互作用 <0.001）。与缬沙坦相比，筛查 NT-proBNP 并未改变沙库巴曲/缬沙坦的治疗效果（p 相互作用 = 0.96）。随机分组后 16 周，与缬沙坦相比，沙库巴曲/缬沙坦使 NT-proBNP 降低 19%（95% CI：14% 至 23%；p < 0.001），男性 (20%) 和女性 (18%) 的降低程度相似，以及左心室 EF ≤ 57% (20%) 和 > 57% (18%) 的患者。NT-proBNP 的下降预示主要终点的后续风险较低。结论 基线 NT-proBNP 可以预测 HF 事件，但不会改变 HFpEF 患者沙库巴曲/缬沙坦的治疗效果。沙库巴曲/缬沙坦在男性和女性以及 EF 较低或较高的患者中一致降低 NT-proBNP。（LCZ696 与缬沙坦相比，对射血分数保留的心力衰竭患者的发病率和死亡率的疗效和安全性 [PARAGON-HF]；NCT01920711）。