Impacts of Febuxostat on Cerebral and Cardiovascular Events in Elderly Patients with Hyperuricemia: Post Hoc Analysis of a Randomized Controlled Trial

Abstract

A recent meta‐analysis found no benefit of uric acid‐lowering therapy including febuxostat on death, cardiovascular events, or renal impairment. However, there may be populations that benefit from febuxostat in reducing mortality and cerebral and cardiovascular events. The aim of the present study was to examine the clinical benefit of febuxostat in elderly patients stratified by age using Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED) data. FREED was a randomized study involving patients aged 65 years or older with hyperuricemia and risk factors for cerebral, cardiovascular, or renal diseases. A total of 1,070 patients were included in this post hoc analysis, divided into 2 age groups: 65–74 years and ≥ 75 years. Patients were randomized into febuxostat and non‐febuxostat groups, with uric acid levels monitored for 36 months. The primary composite end point included cerebral, cardiovascular, and renal events. In patients aged between 65 and 74 years, febuxostat significantly reduced the risk of future cerebral and cardiorenovascular events. However, no effects of febuxostat were found in the older population aged ≥ 75 years. Heterogeneity in potential interactions between the age and febuxostat treatment was particularly observed in non‐fatal cerebral and cardiovascular events and all‐cause death. Patients aged ≥ 75 years exhibited more pre‐existing factors associated with cerebral and cardiorenovascular events than those aged 65–74 years. The effectiveness of febuxostat varies by age group, with potential benefits for patients aged 65–74 years. The effects of febuxostat are complex and it is important to consider patient characteristics in its clinical use.