BACKGROUND Lower estimated glomerular filtration rate (eGFR) may be one of the major reasons for hesitation or failure to initiate potentially beneficial therapies in patients with heart failure (HF). OBJECTIVES This study sought to assess if the effects of sacubitril/valsartan (vs valsartan) on cardiovascular outcomes differ according to baseline kidney function in patients with HF with preserved ejection fraction. METHODS The PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction) trial was global clinical trial of 4,796 patients with chronic HF and left ventricular ejection fraction (LVEF) ≥45% randomly assigned to sacubitril/valsartan or valsartan. We examined the effect of treatment on cardiovascular outcomes using Cox regression models, stratified by region, and assessed for differential treatment effects according to the baseline eGFR and ejection fraction. RESULTS At randomization, mean eGFR was 67 ± 19 mL/min/1.73 m2; 1,955 (41%) participants had an eGFR <60 mL/min/1.73 m2. Compared with valsartan, sacubitril/valsartan reduced the primary cardiovascular outcome (cardiovascular death and total HF hospitalizations) to a greater extent among those with lower baseline eGFR (P interaction = 0.07 for continuous eGFR), and was most pronounced for those with eGFR ≤45 mL/min/1.73 m2 (RR: 0.69; 95% CI: 0.51-0.94). The influence of eGFR on the treatment effect for cardiovascular death was nonlinear, with the most pronounced treatment effect for those with baseline eGFR <45 mL/min/1.73 m2 (HR: 0.65; 95% CI: 0.43-0.97). In further subgroup analyses according to LVEF and eGFR, the treatment effect for the primary outcome was most pronounced among those with LVEF ≤57% and eGFR ≤45 mL/min/1.73 m2 (HR: 0.66; 95% CI: 0.45-0.97). CONCLUSIONS In the PARAGON-HF trial, the benefits of sacubitril/valsartan to reduce the frequency of HF hospitalizations and cardiovascular death were most apparent in patients with lower baseline eGFR and lower ejection fraction. (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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血管紧张素受体脑啡肽酶抑制和肾功能谱的心血管结局：PARAGON-HF 试验。


背景 较低的估计肾小球滤过率 （eGFR） 可能是心力衰竭 （HF） 患者犹豫或未能开始潜在有益治疗的主要原因之一。目的 本研究旨在评估沙库巴曲/缬沙坦 （与缬沙坦相比） 对射血分数保留的 HF 患者心血管结局的影响是否根据基线肾功能不同。方法 PARAGON-HF （射血分数保留的 HF 的 ARNI 与 ARB 总体结局的前瞻性比较） 试验是 4,796 名慢性 HF 患者的全球临床试验，左心室射血分数 （LVEF） ≥45% 随机分配到沙库巴曲/缬沙坦或缬沙坦组。我们使用按地区分层的 Cox 回归模型检查了治疗对心血管结局的影响，并根据基线 eGFR 和射血分数评估了不同的治疗效果。结果 随机分组时，平均 eGFR 为 67 ± 19 mL/min/1.73 m2;1,955 名 （41%） 参与者的 eGFR <60 mL/min/1.73 m2。与缬沙坦相比，沙库巴曲/缬沙坦在基线 eGFR 较低患者中更大程度地降低了主要心血管结局 （心血管死亡和总 HF 住院率） （连续 eGFR 的 P 交互作用 = 0.07），并且在 eGFR ≤45 mL/min/1.73 m2 （RR： 0.69;95% CI： 0.51-0.94） 的患者中最为明显。eGFR 对心血管死亡治疗效果的影响呈非线性，基线 eGFR <45 mL/min/1.73 m2 患者治疗效果最明显 （HR： 0.65;95% CI： 0.43-0.97）。在根据 LVEF 和 eGFR 的进一步亚组分析中，主要结局的治疗效果在 LVEF ≤57% 和 eGFR ≤45 mL/min/1.73 m2 的患者中最为明显 （HR： 0.66;95% CI： 0.45-0.结论 在 PARAGON-HF 试验中，沙库巴曲/缬沙坦降低 HF 住院和心血管死亡频率的益处在基线 eGFR 较低和射血分数较低的患者中最为明显。（与缬沙坦相比，LCZ696 对射血分数保留心力衰竭患者发病率和死亡率的疗效和安全性 [PARAGON-HF];NCT01920711）。