Key result
Higher GDMT score linked to ~6% lower 2-year MACE risk per point across comorbidity domains.
Why the study?
Guideline-directed medical therapy (GDMT) for heart failure reduces major adverse cardiovascular events, but whether cardiac and noncardiac comorbidities influence GDMT effectiveness and dose optimization remains unclear.
Does a higher guideline-directed medical therapy (GDMT) score reduce 2-year major adverse cardiovascular events (MACE) across cardiac and noncardiac comorbidity domains in patients with systolic heart failure (LVEF <50%)?
Cohort (n=2,702)
Yes
Does a higher guideline-directed medical therapy (GDMT) score reduce 2-year major adverse cardiovascular events (MACE) across cardiac and noncardiac comorbidity domains in patients with systolic heart failure (LVEF <50%)?
Higher GDMT dose achievement is associated with reduced 2-year MACE in systolic heart failure regardless of cardiac or noncardiac comorbidity burden, though noncardiac comorbidities hinder optimal dose achievement.
Higher GDMT scores associated with lower MACE across domains; hypothesis-generating for trials targeting noncardiac barriers to optimization.
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.
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Higuchi et al. (2026) conducted a cohort in Systolic heart failure (LVEF <50%) (n=2,702). Guideline-directed medical therapy (GDMT) score (0-12) vs. Lower GDMT score (continuous per point) was evaluated on 2-year major adverse cardiovascular events (MACE), including cardiac death and HF hospitalization (adjusted HR 0.94 per point, 95% CI 0.91-0.98). Higher GDMT scores were associated with a lower 2-year MACE risk (aHR 0.94 per point; 95% CI 0.91-0.98) across both cardiac and noncardiac comorbidity domains.
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