Effects of Sacubitril/Valsartan on Renal Function in Adults With Heart Failure: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Background: We systematically evaluated sacubitril/valsartan (S/V) effects on the renal outcomes of patients with acute or chronic heart failure (HF) receiving angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB). Method: Five (5) databases were searched for randomised controlled trials (RCTs) comparing S/V vs ACEI or ARB in adult patients with HF until 2 September 2023. Doubling of the serum creatinine (sCr) level was the primary outcome. Worsening or decline in renal function (WDRF), >50% decline of estimated glomerular filtration rate (eGFR), and hyperkalaemia (serum K+ >5.5 mmol/L) were secondary outcomes. Inverse variance random-effects meta-analyses were performed, and the effects of S/V on outcomes were described using relative risks (RRs) and their 95% confidence intervals (CIs). Subgroup analyses were performed according to the type of HF (chronic vs acute) and left ventricular ejection fraction (<40% vs >40 %). The GRADE approach was used to rate the certainty of evidence (CoE). Results: Eight (8) RCTs (n=15,859) were included: four on chronic HF and four on acute HF. Median (interquartile range [IQR]) age was 68.4 (63.8–72.7) years in chronic, and 62 (57.1–70.9) years in acute patients, and 34.1% were female. The median (IQR) follow-up was 29.5 (12–108) weeks in chronic and 22 (8–54) weeks in acute patients. In comparison to ACEI or ARB, S/V likely reduced doubling sCr (RR 0.77; 95% CI 0.72 to 0.83; moderate CoE), may have resulted in little to no difference of WDRF (RR 0.88; 95% CI 0.72 to 1.08; low CoE), and had little to no effect on both >50% decline of eGFR (RR 0.65; 95% CI 0.37 to 1.17; very low CoE) and hyperkalaemia (RR 1.01; 95% CI 0.81 to 1.25; very low CoE) but the evidence was very uncertain. Conclusions: In adults with HF, S/V likely reduced doubling sCr compared to ACEI or ARB but may have little to no effect on WDRF, a >50% decline in eGFR, and hyperkalaemia.