Guideline-directed medical therapy implementation and its association with cardiac adverse events across cardiac and noncardiac risk domains

Guideline-directed medical therapy (GDMT) improves prognosis in heart failure (HF), but its implementation remains suboptimal, particularly in patients with multiple risk domains. We analyzed the association between GDMT achievement and the 2-year composite endpoint of cardiac death or HF hospitalization across cardiac and noncardiac risk domains using the WET-HF2 registry, a prospective multicenter Japanese registry. GDMT achievement was quantified using a dose-weighted GDMT score (0-12). Cardiac and noncardiac risk domains were assessed using MAGGIC risk score components. Among 2,702 patients, median GDMT and MAGGIC risk scores were 5 (3-6) and 23 (18-27), respectively. Each 1-point increase in noncardiac risk domain was associated with lower GDMT achievement (adjusted odds ratio [aOR], 0.93; 95% CI 0.90-0.95), whereas each 1-point increase in cardiac risk domain was associated with greater GDMT achievement (aOR, 1.08; 95% CI 1.06-1.10). Among patients in the highest tertile of noncardiac risk, no documented reason for non-prescription of renin-angiotensin system inhibitors or mineralocorticoid receptor antagonists was identified in 11% and 16%, respectively. During 2-year follow-up, 652 patients (24%) experienced the composite endpoint. A higher GDMT score was associated with lower risk of the composite endpoint (adjusted hazard ratio per point, 0.94; 95% CI, 0.91-0.98), consistently across tertiles of cardiac and noncardiac risk (P for interaction=0.784 and 0.359). Higher cardiac risk was associated with greater GDMT achievement, while higher noncardiac risk was associated with lower achievement. The favorable association between GDMT achievement and clinical outcomes was observed across both risk domains.