Effects of SGLT2 inhibitors on hyperuricemia in patients with chronic heart failure with reduced ejection fraction

Background In heart failure, hyperuricemia is common, and higher serum uric acid levels are associated with poorer clinical outcomes. Additionally, hyperuricemia can cause gout, which is difficult to manage and can prolong hospitalization in patients with heart failure. In this context, agents that lower UA have even been investigated as potential treatments for heart failure because of their potential effect on SUA. Purpose Among patients with chronic heart failure, our study aimed to determine whether SGLT2 inhibitor empagliflozin influences SUA levels and whether empagliflozin has therapeutic efficacy related to SUA, particularly their effect on reducing mortality, preventing hospitalization, and improving clinical status. Methods In 164 patients, the association between SUA and cardiovascular death or hospitalization for worsening HF and all-cause mortality was investigated. The treatment effect of empagliflozin was studied in relation to SUA as continuous variable, to clinical hyperuricemia (SUA >5.7 mg/dL for women, >7.0 mg/dL for men). Results Hyperuricemia was prevalent in 61% of patients with no sex differences. Elevated SUA (mean SUA 9.42 ± 1.53 mg/dL) was associated with advanced severity of HF and with worst outcome [composite outcome, hazard ratio (HR) 1.67 (95% confidence interval, CI 1.26–2.14); cardiovascular mortality, HR 1.96 (95% CI 1.32–2.89); all-cause mortality, HR 1.8 (95% CI 1.31–2.44). The reduction of SUA after initiating therapy with empagliflozin was observed rapidly (i.e. at 4 weeks) and was maintained throughout the follow-up period. The beneficial effect of empagliflozin on the primary endpoint was independent of baseline SUA [HR 0.78 (95% CI 0.69–0.90), P < 0.001) and of the change in SUA at 4 weeks [HR 0.84 (95% CI 0.71–0.94), P = 0.014]. Conclusion Hyperuricemia is common in HF and is a strong indicator of advanced disease severity and increased mortality. The administration of empagliflozin resulted in rapid and sustained reductions in SUA levels and hyperuricemia-related clinical events. The benefit of empagliflozin on the primary outcome was observed independently of SUA. Patients with elevated SUA levels experienced a significant reduction in cardiovascular mortality and all-cause mortality, whereas patients with lower SUA levels did not experience this reduction. Empagliflozin was most effective in lowering SUA levels in patients with the highest SUA levels at baseline who also showed the highest mortality risks.Treatment effect of empagliflozin Cumulative incidence of hyperur. events