The Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction (PARAGON-HF) trial demonstrated sacubitril/valsartan modestly lowered total heart failure (HF) hospitalizations and cardiovascular death compared with valsartan in ambulatory HF patients with left ventricular ejection fraction (LVEF) ≥45% 1 Solomon SD McMurray JJV Anand IS et al. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction.

N Engl J Med. 2019; 381: 1609-1620

. Treatment benefits were greater in patients with lower ejection fractions 2 Solomon SD Vaduganathan M L Claggett B et al. Sacubitril/valsartan across the spectrum of ejection fraction in heart failure.

Circulation. 2020; 141: 352-361

and post-hoc analyses identified greater benefit in those with recent HF hospitalization. 3 Vaduganathan M Claggett BL Desai AS et al. Prior heart failure hospitalization, clinical outcomes, and response to sacubitril/valsartan compared with valsartan in hfpef.

J Am Coll Cardiol. 2020; 75: 245-254

That patients with recent HF hospitalization might be an important target population among individuals with heart failure and mildly reduced or preserved ejection fraction is underscored by the potential benefit of sotagliflozin in this population the SOLOIST-WHF trial. 4 Bhatt DL Szarek M Steg PG et al. Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure.

N Engl J Med. 2021; 384: 117-128

Recently, the FDA expanded the indication for sacubitril/valsartan to encompass potentially all patients with chronic HF, although the revised label stated that benefits are most clearly evident in those with an LVEF below normal. In light of these observations, we conducted more detailed analyses of the treatment effects in patients with recent hospitalization in PARAGON-HF, including those with LVEF above the normal range.