Study finds substantial delay in initiation of quadruple guideline-directed medical therapy in patients with HFrEF: JAMA

A new study published in the Journal of the American Medical Association found fewer than 25% (21.2%) of patients—particularly veterans—with heart failure with reduced ejection fraction (HFrEF) to achieve quadruple guideline-directed medical therapy over 2.9 years, with a median time to treatment optimization (TTQ) of 6 months. These results highlight substantial deficiencies in both the adoption and timely initiation of therapy, with medication copays emerging as an important modifiable barrier to better access and improved clinical outcomes.

This research analyzed data from over 52,000 U.S. veterans diagnosed with HFrEF between 2020 and 2023. The focus was on “quadruple guideline-directed medical therapy” (GDMT), which is a combination of 4 key drug classes including β-blockers, renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors. These medications, when used together, are considered the gold standard for managing the condition.

Only 21.2% of patients achieved this comprehensive therapy during a median follow-up of nearly 3 years. Even among those who did, the median time to quadruple therapy (TTQ) was 197 days (over six months) which highlighted the delays in optimizing care.

This study identified Black and Hispanic patients to reach quadruple therapy most likely than White patients, with rates approximately 20% higher after statistical adjustment. The reasons for this disparity remain unclear but may reflect differences in care pathways or targeted clinical efforts within the Veterans Health Administration. However, gender did not significantly impact treatment timelines, with similar rates observed between male and female patients.

The patients required to pay copays were 8% less likely to achieve quadruple therapy when compared to those with no out-of-pocket medication costs. This suggests that even relatively modest financial barriers can delay or prevent access to life-saving treatments.

The patients diagnosed in outpatient settings were more likely to receive full therapy than those diagnosed during hospitalization. Also, individuals with diabetes had higher treatment rates, while those with chronic kidney disease were less likely to reach quadruple therapy, which could possibly be due to the concerns about drug safety or tolerability. Overall, the study illuminates a significant opportunity to improve care delivery for HFrEF patients. 

Reference:

Jacobs, J. A., Greene, T., Vanneman, M. E., Kean, J., Carter, S. J., Shah, K. S., Pandey, A., Derington, C. G., Zheutlin, A. R., Fang, J., Stehlik, J., Fonarow, G. C., & Bress, A. P. (2026). Time to quadruple therapy after initial diagnosis of heart failure with reduced ejection fraction. JAMA Cardiology. https://doi.org/10.1001/jamacardio.2026.0375