Effects of sacubitril valsartan on renal function in adults with heart failure: a systematic review and meta analysis of randomised controlled trials

Abstract Background Sacubitril/valsartan (S/V) may have beneficial effects on renal outcomes in patients with heart failure (HF) receiving angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB). Purpose To systematically evaluate the effects of sacubitril/valsartan on renal function in adults with HF. Methods Five databases were searched for randomised controlled trials (RCTs) comparing S/V (LCZ696) vs. ACEI or ARB in adult HF patients until January 2022. Doubling serum creatinine levels was the primary outcome. Acute kidney injury (AKI)>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 used, and effects of S/V on outcomes were described with relative risks (RR) and their 95% confidence intervals (CI). Subgroup analyses by type of HF (chronic vs. acute), and LVEF (<40% vs >40%) were performed. We used the RoB 2.0 tool for risk of bias assessments of RCTs. GRADE methods were used to rate the certainty of evidence (CoE). Results Eight RCTs (n=15859) were included; four in chronic HF and four in acute HF. Mean age was 66.2 (SD 5.5) years-old, and 34.1% were female. The median follow-up across RCTs was 36 weeks. In comparison to ACEI/ARB, S/V was associated with lower risk of doubling serum creatinine (RR 0.77; 95% CI 0.72–0.83; I2=0%; moderate CoE). S/V did not reduce the risk of AKI (RR 0.88; 95% CI 0.72–1.08; I2=0%; low CoE), >50% decline of eGFR (RR 0.65; 95% CI 0.37–1.17; I2=45%; very low CoE), and hyperkalaemia (RR 1.01; 95% CI 0.81–1.25; I2=44%; very low CoE). Two RCTs had high risk of bias and two had some concerns of bias. Subgroup analyses were consistent with main analyses for the primary outcome. Conclusions In adults with heart failure, S/V reduced doubling creatinine compared to ACEI/ARB, but did not reduce risks of AKI, >50% decline in eGFR or hyperkalaemia. Subgroup analyses by type of HF and LVEF were consistent with main analyses. Funding Acknowledgement Type of funding sources: None.