Abstract 13723: Uric Acid and Treatment With Empagliflozin in Heart Failure With Preserved Ejection Fraction: The EMPEROR-Preserved Trial

Abstract

Background: The sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin reduces CV death and hospitalization for HF (HHF) in patients with HF with preserved ejection fraction (HFpEF). Empagliflozin reduces serum uric acid (SUA), but the relevance of this effect in HFpEF is unclear. Methods: This post-hoc analysis of the EMPEROR-Preserved trial assessed the association between SUA and the composite primary outcome of CV death or hospitalization for worsening HF, its components and all-cause mortality (ACM) in 5,924 patients with HFpEF (98.9% of study cohort). We investigated effects of empagliflozin on SUA levels and hyperuricemic events (acute gout, gouty arthritis or initiation of anti-gout therapy), and on outcomes in relation to baseline SUA and the change in SUA levels Results: Hyperuricemia was prevalent in 49% of patients (male: 42%, female: 57%). Elevated SUA (highest tertile, mean SUA 8.8±1.4mg/dL) was associated with severity of HF and higher risk of HHF (first HHF: HR 1.42 [95%CI 1.08-1.86], recurrent HHF: HR 1.69 [95%CI 1.23-2.32], in comparison with the lowest tertile within the placebo group, both p<0.01). Elevated SUA was not associated with increased CV death and ACM. Empagliflozin reduced SUA at 4 weeks (vs. placebo: -1.0±0.03mg/dL, p<0.0001) and SUA remained lower throughout follow up. Empagliflozin reduced events of clinically relevant hyperuricemia by 38% (HR 0.62 [95%CI 0.51-0.76], p<0.0001). The benefit of empagliflozin on the primary endpoint was independent of baseline SUA (HR 0.79 [95%CI 0.69-0.90], p=0.0007) and absolute change in SUA at 4 weeks (HR 0.87 [95%CI 0.75-1.01, p=0.07] landmark analysis). The benefit of empagliflozin versus placebo on the rate of decline of eGFR and time to first renal composite outcome was consistent across SUA tertiles (p for interaction 0.92 and 0.89, respectively) Conclusion: Hyperuricemia is common in HFpEF and is an independent predictor of disease severity and increased risk of hospitalization. Empagliflozin induced a rapid, sustained reduction of SUA levels and clinical events related to hyperuricemia. The benefit of empagliflozin on the primary outcome in HFpEF was observed independently of SUA.