Underutilization of Guideline-Directed Medical Therapy in Heart Failure With Reduced Ejection Fraction: A Retrospective Study in Rural Appalachia

Introduction: Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) includes a combination of angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB)/angiotensin receptor neprilysin inhibitors (ARNI), beta-blockers, mineralocorticoid receptor agonists (MRA), and sodium-glucose co-transporter 2 inhibitors (SGLT2i). Despite mortality benefits, implementation remains suboptimal. Methods: This was a retrospective observational study conducted in three outpatient Internal Medicine and Cardiology clinics within the East Tennessee State University Health system. Adults aged ≥18 years with ejection fraction (EF) ≤40% and at least one outpatient follow-up between December 2022 and November 2023 were included. Patients with contraindications to GDMT, end-stage renal disease, or limited life expectancy were excluded. GDMT use and dosing (none, <50%, ≥50 to <100%, 100% target dose) for beta-blockers, ACEI/ARB/ARNI, MRA, and SGLT2i were assessed. Descriptive statistics and logistic regression models were used to examine patient characteristics and treatment patterns.

Results: Among 236 eligible patients, only 16.5%, 10.2%, 31.4%, and 42.8% were receiving target doses of beta-blockers, ACEI/ARB/ARNI, MRA, and SGLT2i, respectively. Quadruple therapy was prescribed in just 21.2% of patients, and fewer than 1% achieved target dosing for all four medication classes. MRA use was strikingly low, with 58.9% of patients not on therapy despite its well-established mortality benefit and relative affordability. Multivariable regression analysis revealed several notable associations. Increasing age was linked to lower odds of ACEI/ARB/ARNI use, while higher systolic blood pressure (SBP) favored treatment. MRA use was more likely among patients with lower SBP, non-ischemic cardiomyopathy, obesity, and absence of atrial fibrillation (AF), with obesity and absence of AF being associated with achieving >50% of the target dose. SGLT2i therapy was more common in younger patients with lower ejection fraction and lower SBP, with type 2 diabetes mellitus being the strongest predictor for both initiation and dose optimization. Conclusion: These findings highlight a significant gap in GDMT implementation. Despite favorable patient profiles and a high cost-benefit ratio, MRA use remains limited in this cohort. Targeted interventions to support GDMT initiation and optimization in eligible patients may help reduce disparities in heart failure care.

Keywords: angiotensin receptor-neprilysin inhibitor (arni); angiotensin-converting enzyme inhibitors (acei); angiotensin-ii receptor blocker (arb); beta-blockers; chronic heart failure; guideline-directed medical therapy (gdmt); hfref; mineralocorticoid receptor antagonist; renin-angiotensin-aldosterone system (raas); sglt2-inhibitors.

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