The Association of Guideline-Directed Medical Therapy Scores and Patient Outcomes in Patients With Heart Failure Across the Spectrum of Left Ventricular Ejection Fraction

BACKGROUND: Guideline-directed medical therapy (GDMT) improves outcomes in heart failure with reduced ejection fraction (HFrEF), but its impact in patients with mildly reduced (HFmrEF) or preserved ejection fraction (HFpEF) is less defined. METHODS: We analyzed data from 25,333 adults with ambulatory encounters for heart failure (HF) from February 2022 to February 2024 across >300 clinics in 2 states. Patients were categorized by left ventricular ejection fraction (LVEF) into HFrEF (≤40%), HFmrEF (41-49%), and HFpEF (≥50%), excluding those with improved EF. An electronic health record-embedded GDMT score (range 0-8) was used to quantify therapy with angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blocker (ARB)/angiotensin-receptor neprilysin inhibitor (ARNI), beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors. The primary outcome was a composite of all-cause mortality and hospitalization. RESULTS: The final cohort included 11,810 patients with HFpEF, 2249 patients with HFmrEF, and 6134 patients with HFrEF. GDMT use was highest in HFrEF and lowest in HFpEF. Greater baseline GDMT scores were associated with lower risk of the composite outcome across all EF groups, with the greatest reductions observed at scores ≥6. ACEi/ARB/ARNI and sodium-glucose cotransporter 2 use was associated with lower risk in HFpEF; ACEi/ARB/ARNI, beta-blocker, and mineralocorticoid receptor antagonist use was associated with lower risk in HFmrEF; and all 4 classes were associated with lower risk in HFrEF. ARNI use was associated with better outcomes compared with ACEi/ARB across the EF spectrum. CONCLUSIONS: Comprehensive GDMT was associated with better outcomes across the LVEF spectrum. These findings support the need for prospective evidence to guide medical management in non-HFrEF populations.