Renal protective effect of sacubitril/valsartan in patients with heart failure

Hui-Ling Hsieh,Shih-Chang Hsu,Wen-Cheng Huang,Yuh-Mou Sue,Yue-Cune Chang,Chun-You Chen,Chung-Te Liu,Cheng-Hsien Chen,Feng-Yen Lin,Po-Hsun Huang,Chun-Ming Shih

doi:10.1038/s41598-021-84118-8

Abstract

Sacubitril/valsartan is a combined neprilysin inhibitor/angiotensin II receptor blocker designed for treatment of heart failure (HF). Nonetheless, its renal protective effect remained an issue of debate. This retrospective cohort study investigated the renal protective effect of sacubitril/valsartan in HF patients. HF patients on sacubitril/valsartan or valsartan for > 30 days were matched for gender, age, estimated glomerular filtration rate (eGFR), and left ventricular ejection fraction (LVEF) to be enrolled into analysis. The follow-up period was 18 months. The outcomes included end eGFR, renal function decline defined as 20% reduction of eGFR, mortality, and HF-related hospitalization. Each group had 137 patients after matching. The mean age was 72.7 years and 65.7% were male. Mean eGFR was 70.9 mL/min/1.73 m2 and LVEF was 54.0% at baseline. Overall, the eGFR of sacubitril/valsartan groups was significantly higher than valsartan group at the end (P < 0.01). Subgroup analysis showed that the difference in eGFR was significant in subgroups with LVEF ≥ 40% or eGFR ≥ 60 mL/min/1.73 m2. Multivariate Cox regression model showed that sacubitril/valsartan group had significantly reduced risk for renal function decline (hazard ratio: 0.5, 95% confidence interval: 0.3–0.9). Kaplan–Meier curve showed no difference in the risk for cardiovascular mortality, all-cause mortality or HF-related hospitalization. We showed renal protective effect of neprilysin inhibition in HF patients and specified that subgroups with LVEF ≥ 40% or eGFR ≥ 60 mL/min/1.73 m2 were sensitive to this effect, suggesting an optimal subgroup of this treatment.

Highlights

Heart failure (HF) affects as many as 26 million patients worldwide and has become an important global health issue[1,2]
The present study included two groups of heart failure (HF) patients on sacubitril/valsartan or valsartan, which were matched by gender, age, baseline estimated glomerular filtration rate (eGFR) and left ventricular ejection fraction (LVEF)
In a randomized double-blind trial conducted by the UK HARP-III Collaborative Group, Haynes et al compared the difference of eGFR between patients on sacubitril/valsartan and on irbesartan

Summary

Introduction

Heart failure (HF) affects as many as 26 million patients worldwide and has become an important global health issue[1,2]. In a report released by National Health Insurance of Taiwan, over 22,000 people out of the total 2.3 million population in Taiwan had been hospitalized due to HF in 20144 These reports suggest a huge HF-related medical burden. A designed trial recruiting HF patients with median estimated glomerular filtration rate (eGFR) of 58 mL/min/1.73 m2 showed insignificant difference on renal outcomes, which argues that pre-existing renal impairment may confound renal effect of sacubitril/valsartan[17]. To disclose the renal effects of neprilysin inhibition, a study should be designed to compare the difference between sacubitril/valsartan and valsartan with stratification by the presence of preexisting renal impairment. We hypothesized that sacubitril/valsartan has additional renal protective effect compared with valsartan in patients with subgroups of specific range of renal function. The renal outcomes will be analyzed in subgroups stratified by baseline eGFR to identify patients susceptible to the renal protective effect of neprilysin inhibition

Methods

Results

Conclusion