Abstract 13834: The Effect of Dapagliflozin on Serum Uric Acid in Heart Failure With Reduced Ejection Fraction: Insights From DAPA-HF

Abstract

Introduction: Elevated serum uric acid (sUA) levels are common in patients with heart failure and reduced ejection fraction (HFrEF). sUA, in part, reflects the use of diuretics, and higher sUA is associated with a higher risk of adverse outcomes in HFrEF. We examined the effect of dapagliflozin on sUA, and the efficacy of dapagliflozin according to baseline sUA, in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial. Methods: Patients in NYHA class II-IV with a LVEF ≤40%, and elevated plasma NT-proBNP were included in DAPA-HF. Key exclusions included hypotension, systolic BP <95 mmHg, and eGFR <30 ml/min/1.73m 2 . The primary outcome was a composite of worsening HF (hospitalization for HF or an urgent HF visit requiring iv therapy) or CV death. sUA was measured pre-randomization and at 52 weeks. The effect of dapagliflozin on sUA was assessed using a linear regression model adjusted for baseline value. The efficacy of dapagliflozin was assessed using baseline sUA as a continuous variable. Results: Of the 4744 randomized patients, 3119 (65.7%) had sUA measured at baseline, with a mean of 6.10±1.70 (median 5.9, IQR 4.9-7.1) mg/dL. The placebo-corrected change in sUA at 52 weeks was -0.83 mg/dL (95% CI -0.93, -0.74); p<0.001.In adjusted models including diuretic use/dose, higher sUA was associated with an elevated risk of the primary endpoint; hazard ratio 1.09 (1.03-1.14) per 1mg/dL sUA; p=0.0015 Figure, Panel A .The benefit of dapagliflozin, compared with placebo, on the primary endpoint was consistent across the range of sUA studied ( Figure, Panel B ; P interaction=0.77). Conclusions: In DAPA-HF, higher sUA was associated with worse outcomes and dapagliflozin significantly reduced sUA. The efficacy of dapagliflozin on outcomes was consistent across the range of sUA studied.