Key result
Early SGLT2i initiation in HFrEF linked to ~1.1 percentage point lower 1-year mortality.
Why the study?
Although SGLT2i improve outcomes in patients with HFrEF, the optimal timing of initiation in routine clinical practice remained uncertain.
Does initiation of an SGLT2 inhibitor within 30 days of diagnosis reduce one-year all-cause mortality in adults with incident HFrEF?
Cohort (n=10,346)
Yes
Does initiation of an SGLT2 inhibitor within 30 days of diagnosis reduce one-year all-cause mortality in adults with incident HFrEF?
Early initiation of SGLT2 inhibitors within 30 days of an incident HFrEF diagnosis is associated with significantly lower one-year all-cause mortality and heart failure hospitalization in routine clinical practice.
Early SGLT2i initiation may lower mortality risk; observational data leaves open causality and requires RCTs before practice change.
BACKGROUND AND AIMS: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF), yet the optimal timing of initiation in routine clinical practice remains uncertain. We investigated the impact of early initiation of SGLT2i within 30 days of HFrEF diagnosis on mortality and HF hospitalization. METHODS: Using Danish nationwide register data from July 2020 to August 2024, adults with incident HFrEF eligible for SGLT2i therapy were identified. A target trial comparing initiation of SGLT2i within 30 days of HFrEF diagnosis versus no SGLT2i initiation during this 30-day period was emulated. The analysis used a clone-censor-weight design with follow-up starting at HFrEF diagnosis. The primary outcome was one-year all-cause mortality, and HF hospitalization was assessed as a secondary outcome. RESULTS: Among 10,346 patients with incident HFrEF, 3268 (31.6%) initiated an SGLT2i within 30 days of HFrEF diagnosis and 7078 (68.4%) did not initiate the treatment during this 30-day window. About 226 deaths occurred among SGLT2i initiators and 637 deaths among non-initiators. Compared with non-initiation, initiation of SGLT2i within 30 days was associated with lower one-year risks of both death (RD -1.1 percentage points; 95% CI (-2.0 to -0.2)) and HF hospitalization (RD -3.4 percentage points; 95% CI (-3.9 to -2.9)). CONCLUSIONS: Initiation of an SGLT2i within 30 days of HFrEF diagnosis was associated with lower one-year mortality and HF hospitalization compared with no initiation. These findings support prioritizing early SGLT2i initiation as part of foundational therapy for HFrEF in routine clinical practice.
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Mkoma et al. (2026) conducted a cohort in Incident heart failure with reduced ejection fraction (HFrEF) (n=10,346). Early SGLT2 inhibitor initiation within 30 days of HFrEF diagnosis vs. No SGLT2 inhibitor initiation during the 30-day period after HFrEF diagnosis was evaluated on One-year all-cause mortality (RD -1.1 percentage points, 95% CI -2.0 to -0.2). SGLT2i initiation within 30 days of HFrEF diagnosis was associated with lower 1-year all-cause mortality vs non-initiation (RD -1.1 percentage points; 95% CI -2.0 to -0.2).
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