Efficacy of SGLT2 inhibitors in patients recently hospitalized for heart failure: an exploratory prespecified pooled analysis of the DELIVER and EMPEROR-preserved trials

Background Hospitalization for heart failure identifies patients with preserved ejection fraction (HFpEF) at highest risk. However, precise efficacy estimates for sodium-glucose cotransporter 2 (SGLT2) inhibitors in this vulnerable subgroup—and whether they depend on the definition of “recent” hospitalization—are lacking. Methods This exploratory, hypothesis-generating analysis was a prespecified pooled analysis of the EMPEROR-Preserved and DELIVER trials in patients with HFpEF (LVEF 40%). High-risk subgroups were defined using data from each trial respectively: HF hospitalization within 30 days (“strict”, from DELIVER, n = 654) or 12 months (“broad”, from EMPEROR-Preserved, n = 1,369). The primary endpoint was the composite of cardiovascular death or HF hospitalization. Results Treatment with SGLT2 inhibitors reduced the risk of the primary endpoint by 22% in the strict group (HR: 0.78, 95% CI: 0.60–1.03, with a confidence interval that includes the null) and by 27% in the broad group (HR: 0.73, 95% CI: 0.59–0.90). There was no significant heterogeneity between these estimates ( I ² = 0%), and a similar direction of effect was observed across the two trials. The safety profile was consistent with the known class effect. Conclusion In patients with HFpEF and a recent HF hospitalization, these exploratory findings suggest that SGLT2 inhibitors may provide cardiovascular benefit. The similar direction of effect across two definitions of “recent” (≤30 days and ≤12 months) generates the hypothesis that this high-risk population could benefit, but conclusions are limited by the exploratory, cross-trial design. Further dedicated studies are warranted.