Abstract

Background: Hyperuricemia is associated with poor clinical outcomes in several cardiovascular diseases, including heart failure (HF). However, whether lowering serum uric acid (SUA) levels improves the prognosis of HF remains insufficiently studied.

Aims: To evaluate whether urate-lowering therapy (ULT) with febuxostat confers clinical benefits in patients with HF and concomitant hyperuricemia.

Study Design: Prospective, observational cohort study.

Methods: Patients with chronic HF and hyperuricemia were enrolled and assigned either to a febuxostat group or to a non-ULT group and were followed prospectively for 5 years. The primary endpoint was all-cause mortality or rehospitalization for HF.

Results: Among 2005 patients, those with higher SUA levels experienced more endpoint events. After propensity score matching, we found that febuxostat therapy significantly reduced the incidence of primary endpoints in patients with HFwith preserved ejection fraction (HFpEF) [p = 0.012; hazard ratios (HR), 0.744; 95% confidence intervals (CI), 0.589-0.939], but not in those with HF with reduced ejection fraction (HFrEF) or mildly reduced ejection fraction (HFmrEF) (p = 0.234; HR, 0.894; 95% CI, 0.742-1.077). The benefits of febuxostat in HFpEF were most evident in patients within the highest tertiles of B-type natriuretic peptide (BNP) (p = 0.021; HR, 0.647; 95% CI, 0.436-0.960) and SUA (p = 0.025; HR, 0.651; 95% CI, 0.441-0.963).

Conclusion: High SUA levels are associated with increased all-cause mortality and rehospitalization for HF. Febuxostat-mediated SUA reduction significantly improved clinical outcomes in patients with HFpEF, particularly those with elevated SUA and BNP levels.