Uniform efficacy of SGLT2 inhibitors across the ejection fraction spectrum and in high-risk patients with HFpEF: a prespecified pooled analysis
Abstract
Background: Heart failure with preserved ejection fraction (HFpEF) accounts for over half of all heart failure cases and imposes a high symptom burden. Although SGLT2 inhibitors are guideline-recommended, it remains uncertain whether their efficacy is uniform across the entire LVEF spectrum and in high-risk populations like recently hospitalized patients.
Objective: To definitively assess the consistency of SGLT2 inhibitor efficacy and safety across LVEF subgroups and in extended, high-risk HFpEF populations through a prespecified pooled analysis.
Methods: This trial-level pooled analysis included 12,251 HFpEF patients (LVEF >40%) from the EMPEROR-Preserved and DELIVER trials. Prespecified subgroups were defined by baseline LVEF (2 and interaction tested.
Results: SGLT2 inhibitors significantly reduced the risk of the primary endpoint by 20% vs. placebo (HR 0.80, 95% CI 0.73-0.87, P P = 0.690) and extended to key high-risk subgroups: recently hospitalized patients in DELIVER (HR 0.74) and those with HFimpEF (HR 0.71). No new safety signals were identified.
Conclusion: This analysis confirms a uniform class effect of SGLT2 inhibitors in HFpEF, with consistent cardiovascular protection regardless of LVEF or high-risk clinical status. These findings solidify their role as foundational therapy and support a universal treatment strategy across the ejection fraction spectrum.
Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420261277529,…
How strong is the evidence?
Evidence Hub reads this as a secondary / pooled analysis, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 12,251 participants or records.
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