In-Hospital or Out-of-Hospital Initiation of Sacubitril/Valsartan Versus Valsartan in Patients With Mildly Reduced or Preserved Ejection Fraction After A Worsening Heart Failure Event: The PARAGLIDE-HF Trial.

Abstract

Background: Efficacy and tolerability of sacubitril/valsartan (Sac/Val) is not well characterized in heart failure (HF) with ejection fraction >40% initiated in-hospital. Thus, this prespecified PARAGLIDE-HF (Prospective Comparison of ARNI With ARB Given Following Stabilization In Decompensated HFpEF) analysis assessed the effects of Sac/Val versus valsartan (Val) by location of initiation in HF with ejection fraction >40% and recent worsening HF.

Methods and results: This analysis of the double-blind, randomized controlled trial assessed patients by in-hospital and out-of-hospital (≤30 days of worsening HF) initiation. The primary end point was time-averaged proportional change in NT-proBNP (N-terminal pro-B-type natriuretic peptide) from baseline through weeks 4 and 8. A secondary hierarchical outcome consisted of cardiovascular death, HF hospitalizations, urgent HF visits, and NT-proBNP change. Safety end points were symptomatic hypotension, hyperkalemia, and worsening renal function. Overall, 324 (70%, 162 Sac/Val, 162 Val) were initiated in-hospital and 142 (71 Sac/Val, 71 Val) out-of-hospital. There was no evidence of a statistically significant differential treatment benefit of Sac/Val versus Val on NT-proBNP change by location of initiation (in-hospital, 0.86 [95% CI, 0.70-1.05] and out-of-hospital, 0.87 [95% CI, 0.70-1.09]; P_interaction=0.99). The win ratio for the hierarchical outcome was 1.09 (95% CI, 0.82-1.45; P=0.57) for in-hospital and 1.43 (95% CI, 0.91-2.26; P=0.12) for out-of-hospital. For the safety end points of symptomatic hypotension, hyperkalemia, and worsening renal function, no statistically significant differences in tolerability were seen between in-hospital and out-hospital initiation (P_interaction>0.1).

Conclusions: Sac/Val provided consistent benefit compared with Val, whether initiated in-hospital or out-of-hospital in HF with ejection fraction >40% with a recent worsening HF event, demonstrating an opportunity to improve postdischarge outcomes by initiating Sac/Val during hospitalization.