AIM  To study the safety of clinical application of sacubitril/valsartan (S/V) through meta-analysis.

  METHODS   We searched PubMed, EMBASE, Cochrane Library and Clinical Trials database and results were reported as mean difference (MD), relative ratio (RR) and 95% confidence interval (95% CI).

  RESULTS  A total of 13 randomized controlled trials, 3 cohort studies and 19 observational studies without control group were included. We found that worsening renal function (WRF) events in the S/V group were fewer than those in the renin-angiotensin-aldosterone system inhibitor (RASi) group (RR=0.86, 95% CI: 0.77～0.96, P<0.01). There was no significant difference in hyperkalemia events (blood potassium >5.5 mmol/l) between the two groups (RR=0.98, 95% CI: 0.92～1.05). However, the incidence of severe hyperkalemia events (blood potassium >6.0 mmol/l) in S/V group was significantly lower than that in RASi group (RR=0.82, 95% CI: 0.71～0.95, P<0.01). There was no significant difference in serum creatinine and potassium levels before and after S/V treatment.

  CONCLUSION  Existing evidence has shown that S/V in general is superior to RASi in renal safety. However, since most studies have excluded patients with end stage chronic kidney disease, more clinical studies are still needed to explore its renal safety more comprehensively.