Clinical Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitors Among Older Patients Hospitalized for Heart Failure With Reduced Ejection Fraction

J Am Heart Assoc. 2026 May 19;15(10):e049161. doi: 10.1161/JAHA.126.049161. Epub 2026 May 14.

Abstract

Background: SGLT2 (sodium-glucose cotransporter-2) inhibitors (SGLT2i) reduce cardiovascular events in randomized controlled trials of patients with heart failure with reduced ejection fraction (HFrEF), but these trials enrolled outpatient, relatively younger patients (median age 66-67). The effectiveness of SGLT2i in older patients hospitalized for HFrEF in routine US clinical practice is not well studied.

Methods: This study included Medicare beneficiaries aged ≥65 years hospitalized for HFrEF and eligible for SGLT2i in Get with the Guidelines-Heart Failure between July 1, 2021 and June 30, 2023. Primary outcomes were 30-day and 1-year all-cause mortality, all-cause readmission, and HF readmission. Association between SGLT2i and outcomes was assessed with Cox regression and overlap weighting using propensity score estimates.

Results: A total of 8847 patients were eligible for but not prescribed SGLT2i at hospital admission (Median age 77; 40% women; median left ventricular EF 28%); 1464 (16.5%) patients were initiated on SGLT2i by discharge. After overlap weighting, SGLT2i initiation was independently associated with lower all-cause mortality (adjusted hazard ratio [HR], 0.76 [95% CI, 0.67-0.86]), all-cause readmission (HR, 0.89 [95% CI, 0.81-0.97]), and HF readmission (HR, 0.84 [95% CI, 0.75-0.95]) over 12-month follow-up, compared with those not prescribed SGLT2i. Findings were consistent across subgroups based on age, sex, race, ethnicity, diabetes status, chronic kidney disease status, and left ventricular EF.

Conclusions: Among older patients hospitalized for HFrEF, SGLT2i initiation by time of discharge was independently associated with reduced all-cause mortality, all-cause readmission, and HF readmission. These findings support SGLT2i use to improve postdischarge outcomes among older patients hospitalized for HFrEF in routine US practice.

Keywords: comparative effectiveness research; heart failure; heart failure, systolic; hospitalization; mortality; registries; sodium‐glucose transporter 2 inhibitors.

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Female
  • Heart Failure* / drug therapy
  • Heart Failure* / mortality
  • Heart Failure* / physiopathology
  • Hospitalization
  • Humans
  • Male
  • Patient Readmission / statistics & numerical data
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Stroke Volume* / drug effects
  • Stroke Volume* / physiology
  • Treatment Outcome
  • United States / epidemiology
  • Ventricular Function, Left* / drug effects

Substances

  • Sodium-Glucose Transporter 2 Inhibitors