Sacubitril-valsartan Versus Enalapril or Losartan at Guideline-Recommended Maximum Dosages in Heart Failure with Reduced Ejection Fraction: Real-World Results from the BEAT-HF Cohort

BackgroundSacubitril-valsartan reduced mortality and hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF) compared to enalapril in pivotal clinical trials. However, these studies used suboptimal dosages of enalapril, potentially limiting their findings. ObjectiveTo compare the outcomes of HFrEF patients treated with sacubitril-valsartan versus either enalapril or losartan at guideline-recommended maximum dosages. MethodsWe analyzed data from BEAT-HF, an observational cohort of 2,314 HF patients who received care between Aug/2010 and Jan/2024 at six public hospitals in the Brasilia, Brazil. 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 sub-maximum dosages. The primary outcome was combined hospitalization or death. Baseline differences were adjusted using propensity score matching. ResultsAmong 254 HFrEF patients (mean age 63.6{+/-}12.3 years, 61.4% male), 115 received sacubitril-valsartan 97/103mg twice daily, 33 enalapril 20mg twice daily, and 106 losartan 100mg daily. Over the median follow-up of 23.9 months [IQR 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 significantly reductions in combined hospitalization or death (OR 0.650, 95%CI 0.354 - 1.195, p=0.165), but it was strongly associated with functional status improvement (OR 3.902, 95%CI 1.745 - 8.726, p=0.001). ConclusionThis real-world study wasnt able to support significant reductions in hospitalization or mortality for sacubitril-valsartan compared with enalapril or losartan at guideline-recommended maximum dosages, suggesting that its benefits may be more modest than previously reported.