Abstract
Purpose: To evaluate the renoprotective effect of sacubitril/valsartan (Sac/Val) against angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB). 
 Methods: Following PRISMA guidelines, a thorough search of PubMed, Embase, Web of Science, and Cochrane Library was performed up to May 18, 2023. Eligibility criteria included prospective, randomized, controlled trials comparing sac/Val and ACEI/ARB with regard to renal outcomes. Data extraction and quality assessment were undertaken independently by two reviewers. Fixed or random effects models were used depending on the heterogeneity among studies. Subgroup analyses were performed based on the presence or absence of heart failure. 
 Results: Eleven trials with varied patient populations and clinical settings were included. The meta-analysis revealed that Sac/Val exhibited a significantly reduced risk of renal function decline compared to ACEI/ARB (Risk Ratio (RR) = 0.86, 95 % Confidence Interval (CI) (0.78, 0.96), p = 0.016). Subgroup analysis showed that the renoprotective effect was significant in patients with heart failure (RR = 0.84, 95 % CI (0.75, 0.94), p = 0.011), but not in non-heart failure patients (RR = 1.04, 95 % CI (0.80, 1.37), p = 0.66). 
 Conclusions: This systematic review and meta-analysis suggest that Sac/Val confers substantial renoprotective effect compared with ACEI/ARB, particularly among heart failure patients. However, further research is required to elaborate on the full potential of Sac/Val as a nephroprotective agent.
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