Background The role of neurohormonal inhibition in chronic heart failure (HF) is well established. There are limited data on the effect of up-titration of renin-angiotensin inhibitors (RASi) and beta-blockers (BBs) on clinical outcomes of patients with worsening HF across the left ventricular ejection fraction (LVEF) spectrum.
Methods and results We analysed data from 2345 patients from BIOSTAT-CHF (80.9% LVEF = 100%, 50-99%, 1-49%, and none. Recurrent event analysis using joint and shared frailty models was used to examine the association between RASi/BB dose and all-cause and HF hospitalizations. In the 21 months following up-titration, 512 patients died and 879 (37.5%) had >= 1 hospitalization. RASi up-titration was associated, incrementally, with reduced risk of all-cause hospitalization at all achieved dose levels compared to no treatment [hazard ratio (95% confidence interval): >= 100%: 0.60 (0.49-0.74), P < 0.001; 50-99%: 0.56 (0.46-0.68), P < 0.001; 1-49%: 0.71 (0.59-0.86), P < 0.001]. This association was consistent up to an LVEF of 49% (P < 0.001), and when considering only HF hospitalizations. Up-titration of BBs was associated with fewer all-cause hospitalizations only when LVEF was = 50%. Up-titration of both RASi/BBs was associated with lower mortality in LVEF up to 49%.
Conclusion After recent worsening of HF, up-titration of RASi and BBs was associated with a better prognosis in patients with LVEF = 50%.
- Worsening heart failure
- Renin-angiotensin system inhibitors
- RECURRENT HOSPITALIZATIONS