沙库巴曲缬沙坦在 eGFR<30ml/min/1.73m 患者中的心力衰竭和恶化
Sacubitril/Valsartan in Patients With Heart Failure and Deterioration in eGFR to <30 mL/min/1.73 m.
机构信息
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
出版信息
JACC Heart Fail. 2024 Oct;12(10):1692-1703. doi: 10.1016/j.jchf.2024.03.014. Epub 2024 Jun 5.
BACKGROUND
Sacubitril/valsartan is a foundational therapy for patients with heart failure. Although current U.S. Food and Drug Administration labeling does not provide guidance regarding initiation or continuation of sacubitril/valsartan in patients with worsening kidney function, guidelines identify estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m as a contraindication to therapy.
OBJECTIVES
This study aims to assess the safety and efficacy of continuing sacubitril/valsartan in patients with deterioration of kidney function below an eGFR of 30 mL/min/1.73 m.
METHODS
The association between a deterioration in eGFR <30 mL/min/1.73 m, efficacy and safety outcomes, and treatment with sacubitril/valsartan vs renin-angiotensin system inhibitor were evaluated using time updated Cox models in a post hoc parallel trial analyses of PARADIGM-HF and PARAGON-HF.
RESULTS
Among 8,346 randomized patients in PARADIGM-HF and 4,746 in PARAGON-HF, 691 (8.3%) and 613 (12.9%), respectively, had an eGFR <30 mL/min/1.73 m at least once in follow-up. Patients experiencing such deterioration were at higher risk of the primary outcome in both PARADIGM-HF and PARAGON-HF. However, the incidence of the primary outcome remained lower with sacubitril/valsartan vs renin-angiotensin system inhibitor, regardless of deterioration in kidney function in both PARADIGM-HF (P = 0.50) and PARAGON-HF (P = 0.64). Rates of key safety outcomes were higher among patients experiencing eGFR deterioration; however, rates were similar between treatment groups including among those who remained on treatment.
CONCLUSIONS
Patients experiencing deterioration of kidney function to a value below eGFR 30 mL/min/1.73 m faced high risk of cardiovascular and kidney disease outcomes. Continuation of sacubitril/valsartan was associated with persistent clinical benefit and no incremental safety risk. These data support continuation of sacubitril/valsartan for heart failure treatment even when eGFR declines below this threshold (PARADIGM-HF [Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure], NCT01035255; and PARAGON-HF [Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction], NCT01920711).
背景
沙库巴曲缬沙坦是心力衰竭患者的基础治疗药物。尽管美国食品药品监督管理局目前的标签并未提供有关肾功能恶化患者开始或继续使用沙库巴曲缬沙坦的指导，但指南将估计肾小球滤过率（eGFR）<30 mL/min/1.73 m 确定为治疗的禁忌症。
目的
本研究旨在评估在 eGFR 下降至<30 mL/min/1.73 m 的情况下继续使用沙库巴曲缬沙坦的安全性和疗效。
方法
使用 PARADIGM-HF 和 PARAGON-HF 事后平行试验分析中时间更新的 Cox 模型，评估 eGFR<30 mL/min/1.73 m 恶化、疗效和安全性结局与沙库巴曲缬沙坦与肾素-血管紧张素系统抑制剂治疗之间的关系。
结果
在 PARADIGM-HF 中，8346 名随机患者和 PARAGON-HF 中 4746 名患者中，分别有 691 名（8.3%）和 613 名（12.9%）患者在随访中至少有一次 eGFR<30 mL/min/1.73 m。在这两项研究中，出现这种恶化的患者发生主要结局的风险均较高。然而，无论在 PARADIGM-HF（P=0.50）还是 PARAGON-HF（P=0.64）中，沙库巴曲缬沙坦与肾素-血管紧张素系统抑制剂相比，发生主要结局的发生率仍然较低。在 eGFR 恶化的患者中，关键安全性结局的发生率较高；然而，在包括继续治疗的患者在内的治疗组中，发生率相似。
结论
肾功能恶化至 eGFR<30 mL/min/1.73 m 的患者面临较高的心血管和肾脏疾病结局风险。继续使用沙库巴曲缬沙坦与持续的临床获益相关，且无额外的安全风险。这些数据支持即使 eGFR 下降至该阈值以下，仍继续使用沙库巴曲缬沙坦治疗心力衰竭（PARADIGM-HF [前瞻性比较 ARNI 与 ACEI 对心力衰竭患者全球死亡率和发病率的影响]，NCT01035255；和 PARAGON-HF [前瞻性比较 ARNI 与 ARB 在射血分数保留的心力衰竭中的全球结局]，NCT01920711）。
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