Optimization of Guideline-Directed Medical Therapy in Patients With Heart Failure With Reduced Ejection Fraction

Heart failure with reduced ejection fraction (HFrEF) carries significant morbidity and mortality. The concurrent use of four guideline-directed medical therapy (GDMT) classes, known as quadruple therapy, is associated with significant improvements in mortality. Despite their benefit, utilization is low, but the disparities in optimization, time-to-, and variation in quadruple therapy are largely unknown on a national level.

The objectives of this dissertation are 1) to determine disparities in quadruple therapy optimization by race and ethnicity, sex, and adverse social determinants of health (Aim 1), 2) to characterize time-to-quadruple therapy and factors associated with time-to-quadruple therapy in patients with a new diagnosis of HFrEF (Aim 2), and 3) to determine the variation in time-to-quadruple therapy by clinician and facility-level variables (Aim 3). 

First, 82,637 hospitalized patients with HFrEF were analyzed using the American Heart Association Get With The Guidelines-Heart Failure registry to assess associations between race, ethnicity, sex, insurance type, and social needs with quadruple therapy optimization (QTO). Black, Hispanic, and female patients have higher QTO scores, while those with no insurance, Medicaid, Medicare, or an identified social need have significantly lower QTO scores, underscoring disparities in guideline-directed medical therapy use. 

Next, a retrospective cohort study of 52,756 Veterans Health Administration patients with incident HFrEF (2020–2023) was performed to characterize time-to-quadruple therapy and associated factors using Cox proportional hazards models. Over a mean follow-up of 2.9 years, 21.6% achieved quadruple therapy, with Black and Hispanic patients more likely to do so, while prescription co-pays were associated with a lower likelihood of achievement of quadruple therapy, emphasizing financial barriers to timely therapy initiation.

Using the same cohort of incident HFrEF from the Veterans Health Administration, it was found that two-thirds of the variation in time-to-quadruple-therapy was attributable to clinician variability, one-third to facility differences, and minimal variation due to regional differences.

Overall, this dissertation significantly enhances our understanding of disparities, national quality, and variation in quadruple therapy optimization for patients with HFrEF. It underscores the critical role of social determinants of health in GDMT optimization and identifies key targets for future interventions, including medication coverage, cost, and clinician-directed strategies.