Quadruple therapy was achieved by only 21.2% of patients with HFrEF over a median 2.9 years, with a median time to therapy of 6 months and medication copays acting as a barrier.
Only a minority of HFrEF patients achieve quadruple therapy, highlighting a significant implementation gap where medication copays represent a modifiable barrier.
Absolute Event Rate: 0% vs 0%
IMPORTANCE: Timely prescription of quadruple guideline-directed medical therapies (GDMTs) for patients with heart failure with reduced ejection fraction (HFrEF) is associated with improved morbidity and mortality, yet contemporary estimates of time to quadruple therapy (TTQ) and the factors associated with its achievement remain unknown. OBJECTIVE: To characterize TTQ and factors associated with TTQ in HFrEF. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study including patients with incident HFrEF from the Veterans Health Administration database during the January 1, 2020, to December 31, 2023, period. Study data were analyzed from November 2024 to December 2025. EXPOSURES: Primary factors included race and ethnicity, sex, and copay status (priority group). Secondary factors included clinical characteristics. MAIN OUTCOMES AND MEASURES: The main outcome included quadruple therapy according to pharmacy fill data-concurrent use of evidence-based β-blockers, renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors. TTQ was defined as the first date that all 4 medication classes overlapped, based on dispense date and days' supply. RESULTS: Among 52 850 patients with incident HFrEF (median SD age, 71.8 11 years; 51 473 male 97%; 10 791 Black 20%; 2528 Hispanic 5%; 35 867 White 68%; 3664 other 7%), 11 217 (21.2%) achieved quadruple therapy over a median (IQR) follow-up of 2.9 (1.9-3.9) years. The median (IQR) TTQ was 197 (49-528) days. After adjustment, Black patients (hazard ratio HR, 1.22; 95% CI, 1.15-1.30), Hispanic patients (HR, 1.21; 95% CI, 1.09-1.33), and those from other racial or ethnic groups (HR, 1.11; 95% CI, 1.02-1.20) had higher rates of quadruple therapy than White patients. There was no difference in TTQ in females vs males (HR, 0.97; 95% CI, 0.86-1.09). Prescription copays (priority groups 2-8) were associated with an 8% lower rate of achieving quadruple therapy (HR, 0.92; 95% CI, 0.87-0.96) than no prescription copay (priority group 1). Rates of quadruple therapy were higher among veterans with an outpatient HFrEF diagnosis vs inpatient (22.2% vs 14.2%), with diabetes vs without diabetes (23.6% vs 19.3%), and without chronic kidney disease vs with chronic kidney disease (22.5% vs 18.1%). CONCLUSION AND RELEVANCE: Results of this cohort study suggest that opportunities exist to improve both the rate and timeliness of quadruple therapy as only 21.2% of patients with HFrEF achieved it, with a median follow-up of 2.9 years and TTQ of 6 months. Medication copays represent a modifiable barrier, providing a potential target for interventions to enhance TTQ.
“In HFrEF, the four medications clearly reduce all-cause mortality, are nonoverlapping and truly and fully additive, and their benefits are cumulative, incremental, and begin within days. Yet, when we look at their actual implementation in clinical practice, we've seen this slow and variable uptake.”
This study in JAMA Cardiology highlights significant delays in the initiation of guideline-directed quadruple therapy for HFrEF, sparking conversations about implementation strategies and barriers to optimal heart failure care.
Jacobs et al. (Wed,) reported a other. Quadruple therapy was achieved by only 21.2% of patients with HFrEF over a median 2.9 years, with a median time to therapy of 6 months and medication copays acting as a barrier.