Contemporary Guideline-Directed Medical Therapy Underused in Heart Failure

Results from the EMPACE study have indicated that hospitalized patients with heart failure (HF) demonstrate high comorbidity and low utilization of many guideline-directed medical therapies (GDMTs) prior to hospitalization.

Presented at the 9th Annual Heart in Diabetes Conference, these data indicate a need for further clinical acceptance of GDMT components to reach patients in need.

After rapid therapeutic advances in treating and managing HF in the last 30 years, guidelines developed by cardiology specialists have become extremely robust. However, the advent of GDMT may have overgeneralized heart failure management, overlooking differences in the clinical manifestation of the syndrome in different patients.2

Additionally, the clinically reported efficacy of GDMT components is generally shown in trials with restrictive criteria; this makes it difficult to replicate these results in routine practice. Because of this, more recent studies have indicated that many recommended GDMT components lack unequivocal evidence of clinical efficacy.2

To that end, Stephen J. Greene, MD, associate professor of medicine and cardiology at the Duke Clinical Research Institute, and colleagues conducted the EMPACE (Treatment Patterns of Guideline Directed Medical Therapies in Heart Failure Patients in the Real World) study, aiming to better describe baseline demographics and clinical characteristics of patients hospitalized with HF. Baseline was defined as GDMT and comorbidities characterized 1 year before HF admission.1

EMPACE was a non-interventional, retrospective cohort study that ran from June 2020 to October 2023. Included patients were hospitalized with a primary diagnosis of HF; they were then stratified by HF phenotype based on left ventricular ejection fraction (LVEF) (heart failure with reduced ejection fraction [HFrEF]: LVEF ≤40%, heart failure with mildly reduced ejection fraction [HFmrEF]: LVEF 41%-49%, heart failure with preserved ejection fraction [HFpEF]: LVEF ≥50%). Data was sourced from the Optum’s de-identified Market Clarity Database.1

A total of 30,762 patients were included in the study, with mean age (standard deviation [SD]) 70.1 +/- 13.5 years. Of these, 60% were male, and mean BMI (SD) sat at 30.6 +/- 8.7 A full 90% of patients had a history of hypertension, and 72% had a history of HF diagnosis. After stratification, the HFrEF subgroup included 22,815 patients (74%), the HFmrEF subgroup included 1124 patients (4%), and the HFpEF subgroup included 6823 patients (22%). Most patients had a prior HF diagnosis (72%).1

Investigators noted a high prevalence of comorbidities across all ejection fraction categories (hypertension 89-95%, coronary artery disease 51-58%, atrial fibrillation 39-45%). Despite this, prescription of the majority of newer GDMTs, such as angiotensin receptor-neprilysin inhibitor (ARNI) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), were significantly lower than that of beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARB).1

Beta-blockers, ACE inhibitors, and ARB accounted for the majority of prescriptions (>60% of patients overall), followed by mineralocorticoid receptor antagonist (MRA) (21%). ARNI rate decreased further among those with HFmrEF and HFpEF. SGLT2i usage was similarly low across all ejection fraction categories.1

Greene and colleagues concluded that, given the high comorbidity burden and low GDMT utilization prior to hospitalization, adoption of modern GDMT strategies is still insufficient.

“The strikingly low utilization of MRA and newer therapies such as ARNI and SGLT2i indicate a critical need for strategies to enhance GDMT adoption in clinical practice,” Greene and colleagues wrote.1

References

1. Greene, S, et al. Contemporary Guideline-Directed Medical Therapy in Heart Failure in Clinical Practice: Results from the EMPACE Study. Abstract presented at the 9th Annual Heart in Diabetes Conference in Philadelphia, PA, June 6-8, 2025.

2. Samarendra P. GDMT for heart failure and the clinician's conundrum. Clin Cardiol. 2019;42(12):1155-1161. doi:10.1002/clc.23268