Longitudinal trajectories of guideline-directed medical therapy and 12-month mortality in acute heart failure: insights from the KorHF-III Registry

Background Current guidelines mandate initiating and up-titrating quadruple guideline-directed medical therapy (GDMT) for heart failure (HF). However, real-world data on longitudinal changes in GDMT prescriptions and their impact on long-term survival, particularly in Korean population, remains scarce. We investigated the trajectories of GDMT from hospital discharge to 12 months and their independent association with all-cause mortality. Methods We collected and analyzed data from 7,351 patients admitted for acute HF in the Korean Heart Failure Registry Phase III (KorHF-III) across 47 centers. To eliminate immortal time bias, the primary analysis was restricted to 5,450 patients who survived and had medication data at 12-month follow-up. Based on the number of prescribed GDMT classes (RAS inhibitors, beta-blockers, MRAs, SGLT2 inhibitors), patients were categorized into three trajectory groups from discharge to 12 months: “Intensified” (drug count increased), “Stable” (count unchanged), or “De-escalated” (count decreased). Multivariable logistic regression, adjusting for 11 clinical covariates including age, sex, left ventricular ejection fraction, renal function, and comorbidities, was used to evaluate the association between GDMT trajectory and 12-month all-cause mortality. Results Among 5,450 eligible patients, GDMT was intensified in 17.7%, remained stable in 56.3%, and was de-escalated in 25.9% by 12 months. Crude mortality rates were 10.8% for intensified, 15.1% for stable, and 20.8% for de-escalated groups. After multivariable adjustment (N=1,833 complete cases), GDMT de-escalation was significantly associated with a 68% higher risk of mortality compared to stable GDMT (adjusted Odds Ratio [OR] 1.68, 95% CI 1.28–2.20, p<0.001). Conversely, GDMT intensification was independently associated with a 56% lower risk of mortality (adjusted OR 0.44, 95% CI 0.27–0.71, p<0.001). Despite these benefits, substantial treatment gaps were observed at 12 months, with 37.8% and 27.3% of eligible patients completely lacking RAS inhibitor and beta-blocker prescriptions, respectively, in the absence of documented contraindications. ARNI prescription rates, however, increased by 87% (from 19.1% at discharge to 35.6% at 12 months). Conclusion In a large, contemporary acute HF cohort, over 25% of patients experienced GDMT de-escalation by 12 months, which was independently associated with significantly increased mortality. These findings emphasize the critical need for systematic, longitudinal efforts to sustain and intensify GDMT post-discharge, as substantial, unjustified contraindication-aware treatment gaps persist in routine practice.RESULT