Early initiation of SGLT2i was associated with an 88.1% probability of remaining in a stable heart failure state without hospitalization at 10 years, compared to 58.1% with traditional GDMT.
Cohort (n=10,873)
Does early initiation of SGLT2 inhibitors, ARNI, or full GDMT reduce heart failure hospitalizations and mortality in heart failure patients compared to traditional GDMT?
Early initiation of SGLT2 inhibitors demonstrated the strongest protective effect against heart failure progression and mortality over 10 years in a real-world Southeast Asian cohort, outperforming traditional GDMT.
Absolute Event Rate: 88.1% vs 58.1%
Abstract Background Early initiation of guideline-directed medical therapy (GDMT) plays a crucial role in modifying heart failure (HF) progression, yet real-world adoption of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and angiotensin receptor-neprilysin inhibitors (ARNI) remains limited. While ARNI is primarily recommended for HF with reduced ejection fraction (HFrEF), SGLT2i has shown benefits across all HF phenotypes, including HF with preserved ejection fraction (HFpEF) and HF with mildly reduced ejection fraction (HFmrEF). This study aimed to compare the long-term effects of early SGLT2i and ARNI use versus traditional GDMT in preventing hospitalizations and mortality in a real-world HF population using a multi-state model. Methods This retrospective cohort study analyzed 10,873 HF patients from a real-world Southeast Asian database (2010–2024), excluding those without HF-specific medications. Patients were categorized into four treatment groups based on medications received within 6 months of HF diagnosis: SGLT2i (n=2,263), ARNI (n=346), GDMT (≥1 HF medication, n=7,991), and Full GDMT (SGLT2i + ARNI + β-blockers + mineralocorticoid receptor antagonists, n=273). A multi-state model estimated transition probabilities between clinical states: initial HF, first hospitalization (HFH1), second hospitalization (HFH2), recurrent hospitalization (HFH3+), and all-cause mortality. Results SGLT2i consistently demonstrated the highest probability of keeping patients in a stable HF state without hospitalization. At 10 years, 88.1% of SGLT2i users remained in their initial HF state, compared to 78.3% in Full GDMT, 74.0% in ARNI, and 58.1% in traditional GDMT. The probability of transitioning to first hospitalization (HFH1) was lowest with SGLT2i (4.8%) compared to Full GDMT (5.0%), ARNI (8.6%), and GDMT (14.5%). Mortality risk progressively increased over time, with SGLT2i users having the lowest probability of death (4.8% at 10 years), followed by Full GDMT (7.5%), ARNI (12.1%), and GDMT (39.6%). While Full GDMT provided better outcomes than GDMT alone, it did not outperform SGLT2i alone, which remained the most effective in preventing HF progression and mortality. Conclusion Early initiation of SGLT2i and ARNI significantly reduces HF hospitalizations and mortality compared to traditional GDMT. SGLT2i demonstrated the strongest protective effect across all HF phenotypes, maintaining stability, preventing hospitalizations, and reducing long-term mortality. Full GDMT (SGLT2i + ARNI + β-blockers + MRA) showed better long-term outcomes than GDMT alone but did not surpass the benefits of SGLT2i alone. These findings highlight the need to prioritize early SGLT2i initiation as a cornerstone therapy in HF management, irrespective of ejection fraction.Multi-State Model Transition Diagram Probability of Remaining in HF Over Time
Amornritvanich et al. (Sat,) conducted a cohort in Heart failure (n=10,873). Early initiation of SGLT2i vs. Traditional GDMT was evaluated on Remaining in initial heart failure state without hospitalization at 10 years. Early initiation of SGLT2i was associated with an 88.1% probability of remaining in a stable heart failure state without hospitalization at 10 years, compared to 58.1% with traditional GDMT.