Abstract
Background
The efficacy, safety, and tolerability of an angiotensin receptor-neprilysin inhibitor (ARNi) in patients presenting with de novo heart failure (HF) has not been previously well-defined.
Methods
The PIONEER-HF trial was a prospective, multicenter, double-blind, active-controlled, randomized clinical trial which enrolled 887 patients (pts) at 129 sites in the United States. Pts with or without a history of prior HF and an ejection fraction (EF) <40% and a NT-proBNP >1600 pg/mL or BNP >400 pg/mL were eligible for participation no earlier than 24 hours while still hospitalized for acute decompensated HF (ADHF). Pts were randomly assigned 1:1 to in-hospital initiation of sacubitril/valsartan (S/V) titrated to 97/103 mg vs. enalapril titrated to 10 mg both by mouth twice daily for 8 weeks. We performed a pre-specified analysis in pts with de novo HF (i.e., defined as pts without a history of HF prior to the qualifying ADHF event).
Results
At the time of enrollment, 34% (N=303) had de novo HF. These pts experienced a similar improvement in NT-proBNP with S/V vs. enalapril (Ratio of geometric means 0.65, 95% Confidence Interval [CI] 0.53–0.81; p-value = 0.0002) compared to pts with worsening chronic HF (ratio 0.72 (0.63–0.83, p-value <0.0001) (Figure). In addition, the incidence of worsening renal function, hyperkalemia, and hypotension was comparable with S/V vs. enalapril regardless of whether they were hospitalized for de novo or worsening chronic HF. Finally, there was no interaction (p-value = 0.350) between previous HF status and the effect of S/V on the composite of cardiovascular death or rehospitalization for HF (de novo HF: Hazard Ratio [HR] 0.34, 95% CI 0.11–1.05 vs. worsening chronic HF: HR 0.60, 95% CI 0.39–0.93).
Conclusion
Among patients admitted for ADHF, irrespective of prior HF history, in-hospital initiation of an ARNi led to a greater reduction in natriuretic peptide levels, a comparable safety profile, and a significant improvement in clinical outcomes.
Acknowledgement/Funding
Novartis
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