Contemporary Guideline-Directed Medical Therapy for Heart Failure in the United States: The EMPACE Study

Background

Randomized trials and clinical guidelines support early initiation of guideline-directed medical therapy (GDMT) for heart failure (HF). The EMPACE (Treatment Patterns of Guideline-Directed Medical Therapies in Heart Failure Patients in the Real-World) study examined GDMT use in US clinical practice among patients hospitalized with heart failure (HHF).


Methods

This observational cohort study examined US patient data from Optum’s deidentified Market Clarity database (June 2020–September 2023). GDMT use was assessed in the 12 months before and after HHF. Discontinuation was assessed over 12 months after initiation.


Results

Among 17,210 patients (73% HF with reduced ejection fraction [EF], 4% HF with mildly reduced EF, 23% HF with preserved EF), mean age was 69.2 years, and 60% were male.


Before HHF, among patients with HF with reduced EF (HFrEF), only 1% received quadruple therapy. Use of individual therapies was:


  • beta blockers: 68%
  • angiotensin-converting enzyme inhibitors/angiotensin receptor blockers: 64%
  • mineralocorticoid receptor antagonists: 23%
  • angiotensin receptor-neprilysin inhibitors (ARNI): 14%
  • sodium-glucose cotransporter-2 inhibitor (SGLT2i): 5%

After HHF, GDMT use improved modestly:


  • quadruple therapy: 2%
  • beta blockers: 84%
  • angiotensin-converting enzyme inhibitors/angiotensin receptor blockers: 72%
  • mineralocorticoid receptor antagonists: 38%
  • ARNI: 26%
  • SGLT2i: 13%

Among patients receiving therapy post discharge, mean time-to-initiation was longest for SGLT2i (88 days) and shortest for beta blockers (15 days). Mean time-to-quadruple therapy was 109 days.


12-month discontinuation rates:


  • ARNI: 62%
  • mineralocorticoid receptor antagonists: 57%
  • SGLT2i: 55%
  • beta blockers: 51%

Among patients with HF with mildly reduced EF (HFmrEF) and HF with preserved EF (HFpEF), only 7% each received SGLT2i before HHF compared with 12% and 9% post-HHF (each with mean time-to-initiation 28 days), respectively.


Conclusions

Among patients hospitalized for HFrEF in contemporary US clinical practice, there were significant gaps in prehospitalization quadruple therapy and only modest GDMT improvement post-discharge, with delayed initiation and high discontinuation rates. Similar patterns were observed with SGLT2i among patients with HFmrEF and HFpEF.


Keywords: SGLT2 inhibitors; guideline-directed medical therapy; hospitalization for heart failure; persistence; real-world evidence.


© 2026. The Author(s).

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