Guideline-directed medical therapy and outcomes across cardiac and noncardiac domains in systolic heart failure
S Higuchi, Y Shiraishi, T Kohno, M Kobayashi, M Kitamura, Y Nagatomo, Y Gatate, M Sakamoto, K Miyamoto, S Shoji, S Kohsaka, T YoshikawaAbstract
Background
Guideline-directed medical therapy (GDMT) for heart failure (HF) reduces major adverse cardiovascular events (MACE), including cardiac death and HF hospitalization. However, whether comorbidities influence GDMT effectiveness and dose optimization remains unclear.
Purpose
To determine whether the association between GDMT dose and MACE differs across cardiac and noncardiac comorbidity domains and whether these domains are associated with optimal GDMT dose achievement.
Methods
Using the WET-HF2 registry, a prospective multicenter Japanese HF registry, we evaluated 2-year MACE in patients with left ventricular ejection fraction <50%. MAGGIC risk score components were categorized into cardiac and noncardiac domains. The GDMT score (0–12) was calculated based on target dose achievement for beta-blockers, renin–angiotensin system inhibitors, mineralocorticoid receptor antagonists, and sodium–glucose cotransporter-2 inhibitors. The optimal cutoff was determined using the Youden index. Associations with 2-year MACE and achievement of the optimal cutoff were assessed using multivariable Cox and logistic regression models.
Results
Among 2,702 patients (age 72 ± 14 years; 67% male), median GDMT and MAGGIC scores were 5 (3–6) and 24 (19–28). Two-year MACE occurred in 652 patients (24%). A higher GDMT score was associated with a lower risk of 2-year MACE (adjusted hazard ratio per point 0.94; 95% confidence interval [CI], 0.91–0.98), consistent across tertiles of the overall MAGGIC risk score and its cardiac and noncardiac domains (p for interaction = 0.863, 0.784, and 0.359). The optimal cutoff of the GDMT score for predicting 2-year MACE was 5. A higher noncardiac domain was associated with lower odds of achieving GDMT ≥5 (adjusted odds ratio [aOR] per point 0.93; 95% CI 0.90–0.95), whereas a higher cardiac domain was associated with higher odds of achieving GDMT ≥5 (aOR 1.08; 95% CI 1.06–1.10).
Conclusions
Higher GDMT scores were associated with lower MACE across cardiac and noncardiac domains. The noncardiac domain was inversely associated with GDMT dose achievement, suggesting challenges in dose optimization among those with higher noncardiac domain.Cardiac domainsNoncardiac domains