EMPEROR-Pooled: effect of empagliflozin on serious adverse renal outcomes in chronic heart failure – a prospective alpha-protected, Individual patient-level pooled analysis

Presented at the ESC congress 2021 by: Milton Packer, MD - Dallas, TX, USA

Introduction and methods

EMPEROR-Pooled was a prospectively-designed, patient-level pooled analysis of the data from EMPEROR-Reduced and EMPEROR-Preserved . Both trials investigated the effects of the SGLT2 inhibitor empagliflozin versus placebo in patients with established HF. The primary composite outcome of both trials was time to first event of adjudicated CV death or adjudicated HF hospitalization. EMPEROR-Reduced and EMPEROR-Preserved had nearly identical protocols and were caried out in a similar time period. The trials were primarily distinguished by the LVEF cutoff of 40%: Patients enrolled in EMPEROR-Reduced had HF and an LVEF of ≤40%, while patients enrolled in EMPEROR-Preserved had HF and an LVEF of >40%.

EMPEROR-Pooled assessed the effects of empagliflozin vs placebo on HF hospitalization and major renal outcomes in patients with HF across the entire spectrum of LVEF. A total of 9718 patients were included in the analysis and EMPEROR-Pooled had its own statistical plan, which was defined at the start of the program.

Main results

• Empagliflozin reduced the risk of HF hospitalization to a similar degree in EMPEROR-Reduced and EMPEROR-Preserved. HF hospitalizations were reduced by ~30% by empagliflozin compared to placebo across a range of LVEF from<25% to <65%. Attenuation of the effect was seen at LVEF ≥65%.
• Side-by-side comparison of the results of EMPEROR-Pooled versus PARAGON-HF showed that at LVEF ranging from 40 to 60% the benefit of empagliflozin in EMPEROR-Pooled on time to first HF hospitalization appeared to be greater than with sacubitril/valsartan in PARAGON-HF.
• The effect of empagliflozin on major renal outcomes differed in EMPEROR-Reduced and EMPEROR-Preserved. Empagliflozin significantly reduced the risk of major renal outcomes compared to placebo in EMPEROR-Reduced (HR 0.51, 95%CI 0.33-0.79), but not in EMPEROR-Preserved (HR 0.95, 95%CI 0.73-1.24). The P value for interaction was 0.016.
• LVEF influenced the effects of empagliflozin on major renal outcomes. The effects of empagliflozin versus placebo on renal outcomes in patients with LVEF >40% to <50% were similar to those seen in patients with LVEF ≤40% (HR 0.41, 95%CI 0.20-0.85; and HR 0.52, 95%CI 0.29-0.92, respectively). However, attenuation of the effects of empagliflozin on major renal outcomes was observed at higher LVEF.

Conclusion

The EMPEROR-Pooled analysis showed that the SGLT2 inhibitor empagliflozin, compared to placebo, on top of standard of care reduced HF hospitalizations by approximately 30% in patients with HF across a broad range of LVEF from<25% to <65%. Empagliflozin reduced the risk of major renal outcomes in HF patients with LVEF <50%, but not in patients with higher LVEF.

-Our reporting is based on the information provided at the ESC Congress-

Watch a video by Milton Packer on EMPEROR-Pooled The results of this study were simultaneously published in N. Engl. J. Med.