Rationale, Design and Baseline Characteristics of the PARAGLIDE-HF Trial: Sacubitril/Valsartan vs Valsartan in HFmrEF and HFpEF With a Worsening Heart Failure Event

Background: The PARAGON-HF trial studied the effect of sacubitril/valsartan (Sac/Val) com-pared with valsartan (Val) on clinical outcomes in patients with chronic heart failure with pre-served ejection fraction (HFpEF) or mildly reduced EF (HFmrEF). Further data are needed regarding the use of Sac/Val in these groups with EF and with recent worsening heart failure (WHF) events and in key populations not broadly represented in the PARAGON-HF trial, including those with de novo HF, the severely obese and Black patients.Methods: The PARAGLIDE-HF trial isa multicenter, double-blind, randomized, controlled trial of Sac/Val vs Val that enrolled patients at 100 sites. Medically stable patients > 18 years old with EF > 40%, amino terminal-pro B-type natriuretic peptide (NT-proBNP) levels > 500 pg/mL and within 30 days of a WHF event were eligible for participation. Patients were randomly assigned 1:1 to Sac/Val vs Val. The primary efficacy endpoint is time-averaged pro-portional change in NT-proBNP from baseline through Weeks 4 and 8. Secondary endpoints include clinical outcomes during follow-up and additional biomarker assessments. Safety end-points include symptomatic hypotension, worsening renal function and hyperkalemia.Results: The trial enrolled 467 participants from June 2019 through October 2022 (52% women, 22% Black, age 70 & PLUSMN; 12 years, median (IQR) BMI 33 (27-40) kg/m2). The median (IQR) EF was 55% (50%-60%), 23% with HFmrEF (LVEF 41%-49%), 24% with EF > 60% and 33% with de novo HFpEF. Median screening NT-proBNP was 2009 (1291-3813) pg/mL, and 69% were enrolled in the hospital. Conclusions: The PARAGLIDE-HF trial enrolled a broad and diverse range of patients with heart failure with mildly reduced or preserved ejection fraction and will inform clinical prac-tice by providing evidence about the safety, tolerability and efficacy of Sac/Val vs Val in those with a recent WHF event. (J Cardiac Fail 2023;29:922-930)Key Words: acute decompensated HFpEF, HFmrEF, sacubitril/valsartan, natriuretic peptides, clinical outcomes.