This population-level decision analytic modeling study estimated the number of U.S. adults with HFrEF eligible but not receiving quadruple GDMT (ARNI, beta-blocker, MRA, SGLT2 inhibitor), and projected deaths and hospitalizations preventable with optimal implementation over 12 months, using 2022–2025 national data sources.
Only 18.2% of an estimated 2.76 million eligible U.S. HFrEF adults received quadruple GDMT. Optimal implementation was projected to prevent ~113,747 deaths (95% UI: 90,173–149,875) and ~357,332 HF hospitalizations annually.
Estimates rely on modeled assumptions and trial-derived NNTs applied to real-world populations, which may not fully reflect comorbidity burden or contraindication rates. Treatment rates from Epic Cosmos may not represent all U.S. practice settings. Aggregate death estimates assume independent, additive benefits across drug classes.
More than 1.5–1.8 million HFrEF patients remain untreated for each individual GDMT class — closing these gaps could prevent over 100,000 deaths per year. Clinicians should systematically audit HFrEF patients for GDMT eligibility and prioritize initiation of ARNIs and SGLT2 inhibitors, where gaps are largest.
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