Key result
Triple or quadruple GDMT linked to ~29% lower 1-year mortality in HFrEF versus ≤2 agents.
Why the study?
Comprehensive guideline-directed medical therapy improves survival in HFrEF, but real-world implementation and its longitudinal impact on clinical outcomes remain incompletely characterized.
Does receiving triple or quadruple guideline-directed medical therapy reduce all-cause death and HF re-admission at 1 year compared to receiving ≤2 agents in patients with HFrEF?
Cohort (n=4,010)
Yes
Does receiving triple or quadruple guideline-directed medical therapy reduce all-cause death and HF re-admission at 1 year compared to receiving ≤2 agents in patients with HFrEF?
Real-world implementation of triple or quadruple GDMT in HFrEF patients is associated with reduced 1-year all-cause mortality and HF readmission, though substantial underutilization and treatment de-escalation persist over time.
May encourage GDMT optimization in HFrEF; extends real-world data but leaves causal effects open pending RCTs.
Background/Introduction Comprehensive guideline-directed medical therapy (GDMT) improves survival in heart failure with reduced ejection fraction (HFrEF). However, real-world implementation and its longitudinal impact on outcomes remain incompletely characterized. Purpose This study evaluated temporal trends in GDMT implementation and their association with 1-year clinical outcomes using a large-scale nationwide registry Methods We analyzed patients with HFrEF (left ventricular ejection fraction [LVEF] ≤40%) enrolled in the KorHF III registry. Prescription patterns of four foundational pillars—renin-angiotensin system (RAS) inhibitors, beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), and SGLT2 inhibitors (SGLT2i)—were assessed at discharge and at 1, 3, 6, and 12 months. Patients were categorized by the number of combined therapies. The primary outcomes were all-cause death and HF re-admission at 1 year. Results Among 4,010 patients (age, 65.8 years; 65.7% male; mean LVEF 27.1%), discharge prescription rates were 83.5% for RAS inhibitors, 77.3% for BB, 67.1% for MRA, and 20.8% for SGLT2i. RAS inhibitors and BB prescriptions remained stable, whereas MRA use declined significantly to 54.1% and SGLT2i use increased to 25.7% at 12 months (P for trend<0.001 for both). Over 12 months, MRA use significantly declined to 54.1%, while SGLT2i use increased to 25.7% (both P for trend <0.001). Notably, the proportion of patients receiving triple or quadruple therapy decreased from 55.3% to 50.7% (P for trend = 0.002), whereas those on no therapy increased from 3.3% to 8.1% (P for trend<0.001). Patients receiving triple or more therapies had significantly lower risk of all-cause death (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.59-0.87; P<0.001) and HF re-admission (HR, 0.85; 95% CI, 0.72-1.00; P = 0.049) compared with those receiving ≤2 agents. Conclusion Comprehensive GDMT was associated with significantly improved 1-year survival and reduced HF readmission in HFrEF. Nevertheless, substantial underutilization and treatment de-escalation were observed over time, highlighting a persistent implementation gap in real-world practice.Table.Cox analysis
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Kim et al. (2026) conducted a cohort in Heart failure with reduced ejection fraction (HFrEF) (n=4,010). Triple or quadruple guideline-directed medical therapy (RAS inhibitors, beta-blockers, MRAs, SGLT2 inhibitors) vs. ≤2 guideline-directed medical therapy agents was evaluated on All-cause death and HF re-admission at 1 year (HR 0.71, 95% CI 0.59-0.87, p=<0.001). Triple or quadruple GDMT was associated with lower 1-year all-cause death (HR 0.71; 95% CI 0.59-0.87; P<0.001) and HF readmission (HR 0.85; P=0.049) vs ≤2 agents in HFrEF.
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