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 AND OBJECTIVES: Poor adherence to guideline-directed medical therapy (GDMT) in heart failure with reduced ejection fraction (HFrEF) correlates with increased risks of mortality and hospitalization. Whether it is associated with life-threatening ventricular arrhythmias (VA) remains unclear. We assessed GDMT adherence levels and clinical outcomes in patients with HFrEF. METHODS: Using the National Health Insurance Service database, patients who underwent implantable cardioverter-defibrillator or cardiac resynchronization therapy with a defibrillator implantation between 2008 to 2020 for primary prevention were included. Those with sustained ventricular tachycardia, ventricular fibrillation/flutter, or aborted sudden cardiac death were excluded. Adherence to renin-angiotensin system blockers (RASB), beta blockers (BB), and mineralocorticoid receptor antagonists (MRA) was assessed using the weighted proportion of days covered method. The primary outcome was a composite of all-cause mortality and life-threatening VA. RESULTS: Among 3,780 patients, prescription rates were 87.5% for RASB, 89.7% for BB, and 74.2% for MRA. Poor adherence was associated with an increased risk of the primary outcome (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.31-1.82) and all-cause mortality (HR, 1.83; 95% CI, 1.52-2.20) compared with optimal adherence. These associations were more pronounced in ischemic heart failure (HF). Although crude VA event rates were numerically higher with lower adherence, these associations were insignificant after covariate adjustment, regardless of HF etiology. CONCLUSIONS: Lower GDMT adherence was independently associated with increased mortality despite device therapy, particularly in ischemic HF. Although its relationship with arrhythmic outcomes was unclear, sustained adherence remains important and supports targeted interventions to enhance treatment continuity.