Abstract
BACKGROUND AND AIMS: While sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are known to lower serum uric acid (SUA) in heart failure with reduced ejection fraction (HFrEF) or diabetes, their urate-lowering effect in heart failure with preserved ejection fraction (HFpEF) remains unclear. This study aimed to evaluate this effect in HFpEF patients. METHODS: HFpEF patients newly treated with SGLT-2i were retrospectively included. Changes in SUA level and gout events were analyzed during follow-up. RESULTS: We selected 734 patients according to propensity score matching, with the median age of 75.0(66.0–85.0) years. 31.9% were combined with chronic kidney disease(CKD) and the mean SUA was 6.4 ± 1.9 mg/dl. At 3 to 6-month follow-up, SGLT-2i treatment (79.6% dapagliflozin ) was associated with greater reduction of SUA (-0.91 ± 1.63 mg/dl vs. -0.10 ± 1.54 mg/dl; p < 0.001) and fasting glucose (-0.49(-1.59 to 0.37) vs. 0(-0.83 to 0.39) mmol/l, p = 0.002). 16 cases in SGLT-2i group had gout events and 23 cases in control group (p = 0.25). No significant difference was analyzed in estimated glomerular filtration rate (eGFR) change between groups. The control rate of SUA (< 6 mg/dl) was 72.2% and 51.2% respectively (p < 0.001). Multiple regression analysis suggested that changes of SUA were closely associated with gender, basal SUA level, eGFR and eGFR changes. Subgroup analysis showed that SGLT-2i could reduce SUA regardless of whether combined with diabetes or CKD, and the urate-lowering effect was more pronounced in those with underlying hyperuricemia. CONCLUSION: SGLT-2i (primarily dapagliflozin) could significantly reduce SUA level in HFpEF patients without increasing the risk of gout attack nor injuring renal function.