Effectiveness and risk-benefit analysis of urate lowering therapy in asymptomatic hyperuricemia : a real-world study

Abstract

Hyperuricemia was associated with a higher risk of multiple chronic diseases. Several studies were conducted on urate-lowering therapy agents (ULT) in asymptomatic hyperuricemia, whereas few studies focused on clinical outcomes of cardiovascular events, and as such the treatment effects of ULT on clinical outcomes were inconclusive. Retrospective 10-year observational study (2010 to 2020) was conducted, using electronic medical records of Ramathibodi Hospital of patients with asymptomatic hyperuricemia, who were free of major adverse cardiovascular event (MACE), i.e., acute myocardial infarction, cerebrovascular accident, and cardiovascular death, and renal replacement therapy (RRT) at inception and prescribed with or without any ULT. The interested outcomes were occurrence of MACE, initiation of RRT, progression of chronic kidney disease (CKD), relative changes of estimated glomerular filtration rate (eGFR), serum urate level. The analyses were performed through conventional covariate adjustment and counterfactual approaches. Moreover, risk-benefit analysis was performed to identify the optimal treatment. A total of 23838 patients with asymptomatic hyperuricemia were identified, including 2251 patients in xanthine oxidase inhibitor (XOI) drugs (allopurinol and febuxostat), 150 patients in uricosuric drugs (probenecid, benzbromarone, and sulfinpyrazone), and 21437 patients in no-ULT groups. With conventional covariate adjustment, this study found protective effect of XOI drugs when compared with no-ULT group with adjusted hazard ratios (HR) (95% confidence interval [CI]) of XOI drugs were 0.84 (0.74, 0.96) for MACE prevention, 0.73 (0.56, 0.96) for RRT initiation, and 0.91 (0.83, 0.99) for CKD progression whereas these were not found in uricosuric drugs. By counterfactual approach, preventive effects on MACE, RRT, and CKD progression by XOI as compared to no-ULT were non-significant, whereas XOI resulted in significant higher of eGFR than no-ULT with average treatment effects (95% CI) of 3.27 (2.04, 4.50). Percentage of cardioprotective and renoprotective effects would be higher if clinicians accepted the severe hypersensitivity to be more than 3 and 4 out of 1000 patients, respectively. This real-world evidence suggested that administering XOI drugs in patients of asymptomatic hyperuricemia could lower the risk of developing MACE, RRT initiation, and CKD progression with higher of eGFR compared with no-ULT, whereas these preventive effects were not shown with uricosuric drugs.