Validating the association between a composite metric of guideline-directed medical therapy (GDMT) and clinical outcomes for patients with heart failure with reduced ejection fraction (HFrEF)

Abstract

Abstract Introduction A composite metric to characterize the overall quality of GDMT for patients with HFrEF is important to evaluate quality-of-care and for clinical research. Purpose We sought to evaluate the associations between GDMT scores and cardiovascular outcomes amongst patients with recently-diagnosed HFrEF within a large national integrated health system within the United States. Methods We identified a cohort of patients with recent-onset HFrEF who received care within the Veterans Affairs system between January 2013 and June 2019. We excluded patients with systolic blood pressure <100mmHg or glomerular filtration rate <30 mL/min/1.73m2. We identified active medical therapy based on the last medication fill 90-180 days after the index date (first date with documented HF diagnosis and EF≤40%). We calculated three different GDMT scores: the original Heart Failure Collaboratory Score, the 4-Pillar Intensification Score, and a modified 4-Pillar Intensification Score that included continuous scoring to further incentivize dose uptitration (Figure 1). Using a landmark analysis, we evaluated the association between a 1 standard deviation (SD) change in the GDMT scores at 6 months with the following outcomes: all-cause death, cardiovascular death, and the composite of cardiovascular death/heart failure hospitalization. We repeated the analyses with adjustment for comorbidities and vital signs. Results Among 108,752 patients with recent-onset HFrEF, the mean age was 70.0 years (SD: 11.1) and 97.6% were men. Treatment rates were the following: evidence-based beta-blockers – 55.2%, renin-angiotensin system inhibitors – 60.2%, angiotensin neprilysin inhibitors – 2.9%, mineralocorticoid receptor antagonists – 17.6%, sodium glucose transporter 2 inhibitors – 0.7%, hydralazine/nitrates – 4.9%, and ivabradine – 0.1%. A one standard deviation increase in each of the GDMT scores was associated with improved clinical outcomes (Table 1). Figure 1 illustrates the association between the modified 4-Pillar Intensification Score and the composite of cardiovascular death/heart failure hospitalization. These associations were attenuated but remained significant with comorbidity adjustment. Results also remained consistent when the study period was restricted to 2016 or later and with inclusion of the last prescription fill between 1-180 days post-index date. Conclusion Our study suggests that GDMT scores are consistently associated with clinical outcomes among patients with HFrEF.