Xu Ying, Chen Yang, Zhao Jia Wei, Li Chao, Wang Amanda Y
The Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
The Renal and Metabolic Division, The George Institute for Global Health, University of New South Wales, Newtown, NSW, Australia.
Front Pharmacol. 2021 Nov 19;12:604017. doi: 10.3389/fphar.2021.604017. eCollection 2021.
We aim to perform a systematic review and meta-analysis examining randomized controlled trials assessing the efficacy and safety of sacubitril/valsartan in patients on renal outcomes, in comparison with the renin-angiotensin-aldosterone system inhibitor (RAASi). Eligible studies were retrieved on MEDLINE, EMBASE, and Cochrane until September 2021. The primary outcome was the incidence of renal impairment, which was defined as the composite of increases in serum creatinine by >0.3 mg/dl and/or a reduction in eGFR ≥25%, development of ESRD, or renal death. We pooled relative risks (RRs) with 95% confidence intervals (CIs) or the mean difference with 95% CIs for the variables. Our search yielded 10 randomized controlled trials with a total of 18,362 patients. Compared with RAASi treatment, patients treated with sacubitril/valsartan had lower incidence of composite renal impairment (10 studies, 18,362 patients, RR 0.84; 95% CI 0.72-0.96, = 0.01; = 22%), ESRD development (3 studies, 13,609 patients, RR 0.53; 95% CI 0.30-0.96, = 0.03; = 0%), drug discontinuation due to renal events (4 studies, 9,995 patients, RR 0.58; 95% CI 0.40-0.83, = 0.003; = 47%), severe hyperkalemia (6 studies, 16,653 patients, RR 0.80; 95% CI 0.68-0.93, = 0.01; = 25%) and a slower eGFR decline (4 studies, 13,608 patients, WMD 0.56; 95% CI 0.36-0.76, < 0.00001; = 65%). Subgroup analysis demonstrated that sacubitril/valsartan was associated with a lower incidence of renal impairment in patients with heart failure and preserved ejection fraction (HFpEF), but not in those with heart failure and reduced ejection fraction (HFrEF). The superior renal function preservation of sacubitril/valsartan treatment was not associated with different baseline eGFR levels and follow-up duration. There was a smaller increase in the change in the urine albumin-to-creatinine ratio (UACR) (3 studies, 9,114 patients, SMD 0.06; 95% CI 0.02-0.10, = 0.003; = 14%) with sacubitril/valsartan treatment. However, patients with heart failure appeared to have increased microalbuminuria, not patients without HF ( = 0.80 for interaction). Sacubitril/valsartan was associated with a lower incidence of composite renal impairment especially in patients with HFpEF, but higher microalbuminuria in patients with heart failure (both HFrEF and HFpEF) compared with RAASi. The lower incidence of severe hyperkalemia and drug discontinuation due to renal events in patients with sacubitril/valsartan treatment demonstrated its superior safety compared with RAASi.
我们旨在进行一项系统评价和荟萃分析，以检验随机对照试验，评估沙库巴曲缬沙坦与肾素 - 血管紧张素 - 醛固酮系统抑制剂（RAASi）相比，对患者肾脏结局的疗效和安全性。在MEDLINE、EMBASE和Cochrane数据库中检索截至2021年9月的符合条件的研究。主要结局是肾功能损害的发生率，其定义为血清肌酐升高>0.3mg/dl和/或估算肾小球滤过率（eGFR）降低≥25%、终末期肾病（ESRD）的发生或肾脏死亡的综合情况。我们汇总了各变量的相对风险（RRs）及其95%置信区间（CIs）或均值差及其95% CIs。我们的检索共得到10项随机对照试验，涉及18362例患者。与RAASi治疗相比，接受沙库巴曲缬沙坦治疗的患者复合肾功能损害的发生率较低（10项研究，18362例患者，RR 0.84；95% CI 0.72 - 0.96，P = 0.01；I² = 22%），ESRD的发生率较低（3项研究，13609例患者，RR 0.53；95% CI 0.30 - 0.96，P = 0.03；I² = 0%），因肾脏事件导致停药的发生率较低（4项研究，9995例患者，RR 0.58；95% CI 0.40 - 0.83，P = 0.003；I² = 47%），严重高钾血症的发生率较低（6项研究，16653例患者，RR 0.80；95% CI 0.68 - 0.93，P = 0.01；I² = 25%），且eGFR下降较慢（4项研究，13608例患者，加权均数差（WMD）0.56；95% CI 0.36 - 0.76，P < 0.00001；I² = 65%）。亚组分析表明，沙库巴曲缬沙坦与射血分数保留的心力衰竭（HFpEF）患者肾功能损害发生率较低相关，但与射血分数降低的心力衰竭（HFrEF）患者无关。沙库巴曲缬沙坦治疗在肾功能保护方面的优势与不同的基线eGFR水平和随访时间无关。沙库巴曲缬沙坦治疗使尿白蛋白与肌酐比值（UACR）变化的增加幅度较小（3项研究，9114例患者，标准化均数差（SMD）0.06；95% CI 0.02 - 0.10，P = 0.003；I² = 14%）。然而，心力衰竭患者的微量白蛋白尿似乎有所增加，而非无心力衰竭患者（交互作用P = 0.80）。与RAASi相比，沙库巴曲缬沙坦与复合肾功能损害发生率较低相关，尤其是在HFpEF患者中，但心力衰竭患者（包括HFrEF和HFpEF）的微量白蛋白尿较高。沙库巴曲缬沙坦治疗的患者严重高钾血症和因肾脏事件导致停药的发生率较低，表明其与RAASi相比具有更好的安全性。
