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
M Kim, D H Cho, J Choi, J C Youn, J W Son, J Lee, T Yang, J Oh, C J Lee, B S Yoo, S M KangAbstract
Background
Poor adherence to guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF) is associated with increased risks of mortality and hospitalization. However, its association with malignant arrhythmic events and aborted sudden cardiac death (SCD) remains less well defined, particularly among patients with implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy with defibrillator (CRT-D) for primary prevention.
Methods
We analyzed data from the Korean National Health Insurance Service between 2008 and 2020 and identified patients who had ICD or CRT-D implanted for primary prevention. Those with prior sustained ventricular tachycardia (VT), ventricular fibrillation/flutter (VF/VFL), or aborted SCD device before implantation were excluded. Adherence to renin-angiotensin system blockers (RASB), beta blockers (BB), and mineralocorticoid receptor antagonists (MRA) was assessed using a weighted proportion of days covered (PDC) and categorized as optimal (≥0.8), suboptimal (0.6-0.8), and poor (<0.6). The primary outcome was a composite of all-cause mortality, sustained VT, VF/VFL, and aborted SCD.
Results
Among 3,780 patients (mean age 65.3 years, 66.6% male; median follow-up 3.2 years), prescription rates were 87.5% for RASB, 89.7% for BB, and 74.2% for MRA. Compared with optimal adherence, both suboptimal (aHR 1.24) and poor adherence (aHR 1.54) were associated with increased risk of the primary outcome, with similar stepwise increases for all-cause mortality. The adverse effects of poor adherence were most evident in patients with ischemic HF and other clinically vulnerable subgroups. Although lower adherence appeared to correlate with more arrhythmic events, these associations were not consistent once clinical factors were considered.
Conclusion
Lower GDMT adherence was independently associated with increased mortality despite device therapy, particularly in patients with ischemic HF and vulnerable subgroups. Although the relationship with arrhythmic outcomes was less clear, sustained adherence remains critical, underscoring the need for targeted interventions to enhance therapeutic continuity.Graphical abstractFor image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.