Meta-analysis on the Efficacy and Safety of Sacubitril/valsartan in Heart Failure

14 Oct, 20

Introduction

The superior efficacy of sacubitril/valsartan over angiotensin?converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in patients with heart failure (HF) and hypertension has been already established. Nevertheless, the current evidence on efficacy and safety of sacubitril/valsartan in patients with HF is heterogeneous.

Aim

To assess and compare the effect and adverse events of sacubitril/valsartan, valsartan, and enalapril in patients with HF

Methods

Study Design

Meta-analysis

Study Selection and Analysis

Randomized controlled trials (RCTs) related to the use of sacubitril/valsartan in patients with HF were included in the mate-analysis.
The pooled odds ratio (OR) of all?cause mortality, cardiovascular (CV) mortality, and hospitalization for HF were calculated using fixed?effects models.
The pooled risk ratio (RR) of symptomatic hypotension, worsening renal function, and hyperkalaemia were calculated using fixed?effects models.

Results

Six appropriate studies providing data for 14959 patients were included in this meta-analysis.
Sacubitril/valsartan treatment was associated with reduced risk of all?cause mortality and CV mortality in patients with HF with reduced ejection fraction (HFrEF) in three trials; pooled ORs of 0.83 (P = 0.0006; P=0.64 for heterogeneity; I² = 0%)) and 0.78 (P < 0.0001; P = 0.43 for heterogeneity; I² = 0%), respectively.
Sacubitril/valsartan was associated with a 21% reduction in the risk of the composite outcome of hospitalization for HF in five trials: pooled OR; 0.79 (P < 0.00001; P = 0.51 for heterogeneity; I² = 0%). As per subgroup analyses; the use of sacubitril/valsartan exhibited similar benefits in reducing the composite risk of hospitalization for HF in patients with HFrEF and in those with HF with preserved ejection fraction (HFpEF)
Sacubitril/valsartan was associated with a high risk of symptomatic hypotension when compared with enalapril or valsartan (RR 1.47, P < 0.00001; P= 0.49 for heterogeneity; I²=0%). Sacubitril/valsartan was associated with a lower risk for worsening renal function (RR 0.81, P =0.005; P= 0.77 for heterogeneity; I²=0%), and low rate of serious hyperkalaemia (≥6.0 mmol/L) (RR 0.76, P = 0.0007; P= 0.95 for heterogeneity; I²=0%) when compared with enalapril or valsartan in all six trials.

Conclusions

Compared with ACE inhibitors or ARBs, sacubitril/valsartan significantly decreased the risk of all-cause mortality or CV mortality in patients with HFrEF and hospitalization for HF in patients with HFrEF and those with HFpEF.
Sacubitril?valsartan reduced the risk of renal dysfunction and serious hyperkalaemia, though it was associated with more symptomatic hypotension as compared with ACE inhibitor or ARBs.

ESC Heart Failure. Sep 25, 2020 (Published Online); DOI: 10.1002/ehf2.12974.