Efficacy and safety of sacubitril-valsartan versus enalapril in patients with heart failure due to Chagas cardiomyopathy: a systematic review and meta-analysis
E Begic, D Navalha, L Garcez, A Ferreira, N Costa, O Bisneto, B AziriAbstract
Background
In patients with heart failure with reduced ejection fraction (HFrEF), the angiotensin receptor-neprilysin inhibitor sacubitril-valsartan has consistently demonstrated a beneficial therapeutic effect, vastly in non-Chagas trials. Less is known about the efficacy and safety of sacubitril-valsartan compared with standard of care in patients with Chagas cardiomyopathy, a common but often neglected etiology of nonischemic HFrEF.
Purpose
We aimed to perform a systematic review and meta-analysis to investigate whether sacubitril-valsartan is superior to enalapril in patients with heart failure (HF) due to Chagas cardiomyopathy.
Methods
PubMed, Embase and Cochrane database were searched for randomized controlled trials (RCTs) that compared sacubitril-valsartan with enalapril in patients with HF due to Chagas cardiomyopathy. Efficacy outcomes were (1) cardiovascular (CV) death; (2) HF hospitalization; (3) relative change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline; and safety outcomes were (4) serious adverse events (SAEs); and (5) drug discontinuation due to adverse events (AEs). Cochrane's Review Manager Version 7.2.0 (RevMan, 2024) was used for all statistical analyses. Heterogeneity was examined with I² statistics. Hazard ratios (HR), risk ratios (RR), and mean differences (MD) with 95% confidence intervals (CIs) were pooled using an inverse-variance random-effects model.
Results
Three RCTs comprising 1,112 patients were included, of whom 463 (38%) were females. A total of 615 (50.02%) patients received sacubitril–valsartan, while 610 (49.8%) were treated with enalapril. The mean age was 63.67±10.6 years, and the mean left ventricular ejection fraction (LVEF) was 29.8%±7.2%. There was no statistically significant difference in CV death (HR 0.92; 95% CI 0.72 to 1.18; p=0.51; I²=0; Figure 1A) and HF hospitalization (HR 0.93; 95% CI 0.72 to 1.20; p=0.59; I²=0; Figure 1B) between sacubitril-valsartan and enalapril groups. However, there was a statistically significant reduction in NT-proBNP favoring enalapril over sacubitril-valsartan (MD 0.68; 95% CI 0.63 to 0.73; p<0.00001; I²=0; Figure 1C). No statistically significant difference in SAEs was found between the two treatment arms (RR 0.90; 95% CI 0.79 to 1.03; p=0.12; I²=0; Figure 2A), but there was a trend towards fewer drug discontinuations due to AEs with sacubitril–valsartan compared with enalapril (RR 0.51; 95% CI 0.26 to 1.01; p=0.05; I²=32% Figure 2B).
Conclusion
In this meta-analysis of 1,112 patients with HF due to Chagas cardiomyopathy, sacubitril-valsartan did not statistically significantly reduce CV death or HF hospitalization, relative to enalapril. There was a significant difference between groups in terms of NT-proBNP reduction favoring enalapril. Moreover, sacubitril-valsartan was not superior to enalapril with respect to safety outcomes.Figure 1.Efficacy outcomes.For image description, please refer to the figure legend and surrounding text.Figure 2.Safety outcomes.For image description, please refer to the figure legend and surrounding text.