SGLT2 inhibitors reduced the risk of cardiovascular death or hospitalization for heart failure by 20% compared to placebo in patients with HFpEF (HR 0.80).
Systematic Review (n=12,251)
Yes
Do SGLT2 inhibitors reduce cardiovascular death or heart failure hospitalization in patients with HFpEF across the entire LVEF spectrum and in high-risk subgroups?
This pooled analysis confirms that SGLT2 inhibitors provide consistent cardiovascular protection in HFpEF regardless of left ventricular ejection fraction (including LVEF ≥60%) or high-risk clinical status.
Effect estimate: HR 0.80 (95% CI 0.73–0.87)
p-value: p=<0.001
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 (50%, 50-59%, ≥60%), hospitalization status, and HFimpEF. The primary endpoint was cardiovascular death or heart failure hospitalization. Treatment effect consistency was assessed using an inverse-variance weighted fixed-effects model, with heterogeneity quantified by I 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 0. 001). This benefit was consistent across all LVEF subgroups (50%: HR 0. 76; 50-59%: HR 0. 79; ≥60%: HR 0. 82; interaction 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/displayᵣecord. php? ID=CRD420261277529, PROSPERO CRD420261277529.
Xue et al. (2026) conducted a systematic review in Heart failure with preserved ejection fraction (HFpEF) (n=12,251). SGLT2 inhibitors vs. Placebo was evaluated on Cardiovascular death or hospitalization for heart failure (HR 0.80, 95% CI 0.73–0.87, p=<0.001). SGLT2 inhibitors reduced the risk of cardiovascular death or hospitalization for heart failure by 20% compared to placebo in patients with HFpEF (HR 0.80).