Comparative clinical outcomes on renal function and mortality of uricosuric agents versus xanthine oxidase inhibitors in patients with hyperuricemia and cardiovascular risks

Background High serum uric acid (UA) levels are associated with all-cause death, cardiovascular (CV) events, and a high incidence of chronic kidney disease (CKD) progression. There are unresolved issues regarding whether hyperuricemia plays a causative role or is merely an indirect biomarker of CKD. Hyperuricemia can be caused by UA overproduction or decreased UA excretion. Correspondingly, there are two types of drugs for these conditions: xanthine oxidase inhibitors (XOIs) and uricosuric drugs. Purpose Our study aims to provide valuable real-world perspectives on the influence of UA-lowering therapy on mortality and renal outcomes in patients with hyperuricemia and CV comorbidities. Methods This multicenter retrospective observational study, using TriNetX, a global healthcare data and analytics platform, included patients with hyperuricemia and CV comorbidities who had received XOIs or uricosuric drugs from January 1, 2017, to December 31, 2021. The primary outcome was the 3-year incidence of all-cause death. The secondary outcome was major adverse kidney events (MAKEs). We used odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate outcome measures. Results Among 216,206 patients with hyperuricemia (UA > 7.0 mg/dL) and CV risks, 200,184 initiated XOIs and 16,022 initiated uricosuric drugs. After propensity score matching, the number of participants in both the XOIs and uricosuric drug groups was 14,702. The proportion of 3-year incidence of all-cause death was lower in the uricosuric drug group than in the XOIs group (4.7% [692/14,702] versus 6.2% [913/14,702]; OR, 0.75 [95% CI, 0.67–0.83]). The proportion of 3-year incidence of 4-point MAKEs (dialysis, end-stage renal disease, estimated glomerular filtration rate < 15 mL/min/1.73 m², and mortality) was also lower in the uricosuric drug group than in the XOIs group (13.5% [1,992/14,702] versus 15.6% [2,296/14,702]; OR, 0.85 [95% CI, 0.79–0.90]). Conclusions The use of uricosuric drug therapy is associated with a significantly lower risk of all-cause death and kidney-related events compared with XOIs in hyperuricemia and CV high-risk patients over a 3-year period.