Patterns of Adherence and Persistence to Triple and Quadruple Guideline‐Directed Medical Therapy Among US Patients With Heart Failure With Reduced Ejection Fraction

Background Guideline‐directed medical therapy (GDMT) reduces morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF) if patients adhere to their prescribed regimen. The objectives of this retrospective observational cohort study were to (1) describe adherence and persistence to triple and quadruple GDMT among patients with HFrEF and (2) identify factors associated with heterogeneity in GDMT discontinuation patterns. Methods Patients with HFrEF who had ≥2 prescription fills of triple and quadruple GDMT between January 2021 and December 2022 were identified using Optum's deidentified Clinformatics Data Mart. Outcome measures included adherence to triple and quadruple GDMT and the pattern of discontinuation over time. A latent trajectory analysis identified groups of patients with similar patterns of GDMT discontinuation, and characteristics associated with group assignment were evaluated using logistic regression. Results Of 107 849 patients with HFrEF, 13 304 (12.3%) received triple GDMT and 2478 (2.3%) received quadruple GDMT; 45.0% and 40.8%, respectively, were adherent to the regimens, whereas 21.0% and 17.5%, respectively, discontinued. Two latent classes of treatment trajectories, labeled early discontinuers and persistent GDMT patients, were identified for both triple and quadruple GDMT. Early discontinuation of therapy was identified in 1393 (10.5%) of patients on triple GDMT and 294 (11.9%) of patients on quadruple GDMT. Patient profiles of discontinuation varied between the cohorts. Conclusions Despite evidence and guideline recommendations, adherence to triple and quadruple GDMT in patients with HFrEF was suboptimal. Patients with early discontinuation of GDMT had distinct profiles of sociodemographic, clinical, and health care characteristics. These findings suggest that new strategies are needed to improve initiation and adherence to GDMT to optimize clinical outcomes.