Association of poor adherence to guideline-directed medical treatment with adverse events including fatal arrhythmia in heart failure with reduced ejection fraction: A nationwide cohort analysis

Background: Poor adherence to guideline-directed medical therapy (GDMT) in patients with heart failure (HF) with reduced ejection fraction is associated with higher mortality and hospitalization. However, its association with malignant arrhythmias and aborted sudden cardiac death (SCD) remains unclear. This study assessed the association between GDMT adherence and these outcomes in patients with an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy with a defibrillator (CRT-D). Methods: Patients who had an ICD or CRT-D implanted for primary prevention were included. Those with sustained ventricular tachycardia (VT), ventricular fibrillation/flutter (VF/VFL), or an aborted SCD device before implantation were excluded. Adherence to renin-angiotensin system blockers (RASBs), beta blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) was assessed and categorized as optimal, suboptimal, or poor. The primary outcome was a composite of all-cause mortality, sustained VT, VF/VFL, and aborted SCD. Results: Among 3,780 patients, the prescription rates were 87.5% for RASBs, 89.7% for BBs, and 74.2% for MRAs. Compared with optimal adherence, both suboptimal and poor adherence were associated with an increased risk of the primary outcome. The adverse effects of poor adherence were most evident in patients with ischemic HF. Although lower adherence was correlated with more arrhythmic events, these associations were inconsistent when clinical factors were considered. Conclusions: Lower GDMT adherence was independently associated with increased mortality despite device therapy, particularly in patients with ischemic HF. Although its relationship with arrhythmic outcomes was unclear, sustained adherence remains critical, underscoring the need for targeted interventions to enhance therapeutic continuity.