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

• DOI: 10.1161/jaha.124.037899
• Publication Date: 2025-02-19T11:37:31Z
• Authors: Nina Nouhravesh; Derek Cyr; Adrian F. Hernandez; David A. Morrow; Eric J. Velazquez; Jonathan Ward; Samiha Sarwat; Kavita Sharma; Kristin Williamson; Randall C. Starling; Serge Lepage; Shelley Zieroth; Scott D. Solomon; Robert J. Mentz
• Keywords: Sacubitril; Tolerability; Sacubitril, Valsartan; Clinical endpoint

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 ARNI With ARB Given Following Stabilization In Decompensated HFpEF) analysis assessed the effects Sac/Val versus valsartan (Val) by location initiation HF recent worsening HF. Methods Results This double‐blind, randomized controlled trial patients in‐hospital out‐of‐hospital (≤30 days HF) initiation. The primary end point was time‐averaged proportional change NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) from baseline through weeks 4 8. A secondary hierarchical outcome consisted cardiovascular death, hospitalizations, urgent visits, change. Safety points were symptomatic hypotension, hyperkalemia, renal function. Overall, 324 (70%, 162 Sac/Val, Val) 142 (71 71 out‐of‐hospital. There no evidence a statistically significant differential treatment benefit Val on (in‐hospital, 0.86 [95% CI, 0.70–1.05] out‐of‐hospital, 0.87 0.70–1.09]; P interaction =0.99). win ratio for 1.09 (95% 0.82–1.45; =0.57) 1.43 0.91–2.26; =0.12) For safety function, differences seen between out‐hospital ( >0.1). Conclusions provided consistent compared Val, whether or event, demonstrating an opportunity to improve postdischarge outcomes initiating during hospitalization.