Angiotensin Receptor Neprilysin Inhibition and Cardiovascular Outcomes Across the Kidney Function Spectrum: The PARAGON-HF Trial.

IF 10.3 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS JACC. Heart failure Pub Date : 2024-11-06 DOI:10.1016/j.jchf.2024.08.022

Finnian R Mc Causland, Muthiah Vaduganathan, Brian Claggett, Mauro Gori, Pardeep S Jhund, Martina M McGrath, Brendon L Neuen, Milton Packer, Marc A Pfeffer, Jean L Rouleau, Michele Senni, Karl Swedberg, Faiez Zannad, Michael Zile, Martin P Lefkowitz, John J V McMurray, Scott D Solomon

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Abstract

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).

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血管紧张素受体肾素抑制剂与肾功能范围内的心血管预后：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）患者犹豫不决或无法开始潜在有益治疗的主要原因之一：本研究旨在评估射血分数保留的心力衰竭患者的基线肾功能不同，沙库比特利/缬沙坦（vs 缬沙坦）对心血管预后的影响是否不同：PARAGON-HF（前瞻性比较ARNI与ARB对射血分数保留型心房颤动患者的总体疗效）试验是一项全球性临床试验，共有4796名左心室射血分数（LVEF）≥45%的慢性心房颤动患者随机分配接受了沙格列普利/缬沙坦或缬沙坦治疗。我们使用Cox回归模型研究了治疗对心血管预后的影响，按地区进行了分层，并根据基线eGFR和射血分数评估了不同的治疗效果：随机化时，平均 eGFR 为 67 ± 19 mL/min/1.73 m2；1,955 名参与者（41%）的 eGFR 为 2。与缬沙坦相比，在基线 eGFR 较低的参与者中，沙库比曲/缬沙坦能更大程度地降低主要心血管结局（心血管死亡和 HF 住院总次数）（连续 eGFR 的 P 交互作用 = 0.07），在 eGFR ≤45 mL/min/1.73 m2 的参与者中效果最明显（RR：0.69；95% CI：0.51-0.94）。eGFR对心血管死亡的治疗效果的影响是非线性的，基线eGFR为2的患者治疗效果最明显（HR：0.65；95% CI：0.43-0.97）。在根据 LVEF 和 eGFR 进行的进一步亚组分析中，LVEF ≤57% 和 eGFR ≤45 mL/min/1.73 m2 的患者对主要结局的治疗效果最为显著（HR：0.66；95% CI：0.45-0.97）：在PARAGON-HF试验中，在基线eGFR较低和射血分数较低的患者中，沙库比妥/缬沙坦对降低HF住院频率和心血管死亡的益处最为明显。(LCZ696与缬沙坦相比对射血分数保留的心衰患者发病率和死亡率的有效性和安全性[PARAGON-HF]；NCT01920711）。

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来源期刊

JACC. Heart failure CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

21.20

自引率

2.30%

发文量

164

期刊介绍： JACC: Heart Failure publishes crucial findings on the pathophysiology, diagnosis, treatment, and care of heart failure patients. The goal is to enhance understanding through timely scientific communication on disease, clinical trials, outcomes, and therapeutic advances. The Journal fosters interdisciplinary connections with neuroscience, pulmonary medicine, nephrology, electrophysiology, and surgery related to heart failure. It also covers articles on pharmacogenetics, biomarkers, and metabolomics.