Addressing modifiable barriers such as medication copays may improve access to care and outcomes for patients with heart failure with reduced ejection fraction (HFrEF), according to a cohort study published April 1 in JAMA Cardiology, which identified significant gaps in the rate and timeliness of quadruple therapy for veterans who are newly diagnosed.

The retrospective study used the Veterans Health Administration (VHA) to collect data on 52,850 patients (97% male, 68% White, median age of 71 years) with incident HFrEF from Jan. 1, 2020, through Dec. 31, 2023. Primary factors included race and ethnicity, sex and copay status, and secondary factors were clinical characteristics. Study data were analyzed from November 2024 through December 2025.

Joshua A. Jacobs, PharmD, PhD, et al., established the primary outcome as achievement of quadruple therapy, defined as taking all four guideline-directed medical therapy (GDMT) classes concurrently: evidence-based beta-blockers, renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists and SGLT2 inhibitors, regardless of dose. Time to quadruple therapy (TTQ) was defined as the first date that all four medication classes overlapped.

Over a median follow-up of 2.9 years, only 21% (n=11,217) of patients achieved the primary outcome, with a median TTQ of 197 days. Of note, after adjustment, Black patients (hazard ratio [HR], 1.22), Hispanic patients (HR, 1.21), and patients from other ethnic groups (HR, 1.11) had higher rates than White patients of receiving quadruple therapy. There was no difference in TTQ between men and women.

Moreover, veterans who faced prescription copays were less likely to receive quadruple therapy (HR, 0.92).

Quadruple therapy was more common among patients diagnosed with HFrEF in outpatient settings vs. inpatient settings (22% vs. 14%), among those with diabetes vs. without diabetes (24% vs. 19%) and among those without chronic kidney disease vs. with chronic kidney disease (23% vs. 18%).

“Our findings align with prior work demonstrating variation in GDMT use across patient subgroups, while also revealing important differences related to the setting of diagnosis,” write the authors. They emphasize that out-of-pocket costs and medication coverage “remain important considerations for GDMT uptake within the VHA.”

“By measuring, reporting, and incentivizing reductions in [quadruple therapy] time, health systems and policymakers can catalyze improvements in treatment quality and outcomes for patients with HFrEF,” write Neil M. Kalwani, MD, FACC; Jessica R. Golbus, MD; and Stephen J. Greene, MD, in an accompanying editorial. “To approach HFrEF with the urgency it deserves, we must recognize the need for speed in treatment.”