Renato de Carvalho Barros et al. Vinícius C. Fiusa Gabrielle N. Tim Victoria T. V. Goulart … Caio Henrique M. Nascimento Gustavo T. de Moura Adriana J. B. A. Guimarães Sergio Henrique Rodolpho Ramalho Armindo Jreige Jr. Filipe A. Moura Luiz Sérgio Fernandes de Carvalho
Abstract
Background:
Sacubitril/valsartan reduced mortality and hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF) compared to enalapril in pivotal clinical trials. However, real-world data under optimized dosing remain limited.
Objective:
To compare the outcomes of HFrEF patients treated with sacubitril/valsartan versus either enalapril or losartan at guideline-recommended maximum dosages.
Methods:
We analyzed data from an observational heart failure cohort (n = 2,314) including patients receiving care between August 2010 and September 2024 at six public hospitals in a large metropolitan area. The primary analysis included 254 HFrEF patients receiving the guideline-recommended maximum dosages of the investigated drugs. A sensitivity analysis included 452 patients receiving any submaximal dosages. The primary outcome was combined hospitalization or death. Baseline differences were adjusted using propensity score matching. A p-value < 0.05 was considered significant.
Results:
Among 254 HFrEF patients (mean age 63.6 ± 12.3 years, 61.4% male), 115 received sacubitril/valsartan 97/103mg twice daily, 33 enalapril 20 mg twice daily, and 106 losartan 100 mg daily. Over the median follow-up of 23.9 months (interquartile range 11.9–41.1), there were 70 primary endpoint events (56 first hospitalizations, 32 deaths). Compared to equivalent dosages of enalapril or losartan, sacubitril/valsartan was not associated with significant reductions in combined hospitalization or death (odds ratio 0.650, 95% confidence interval 0.354–1.195, p = 0.165), but it was associated with functional status improvement (odds ratio 3.902, 95% confidence interval 1.745–8.726, p = 0.001).
Conclusion:
This real-world study did not demonstrate significant reductions in hospitalization or mortality for sacubitril/valsartan compared with enalapril or losartan at guideline-recommended maximum dosages; however, sacubitril/valsartan was associated with improved functional status.
