Objectives To compare the risk of urolithiasis in gout patients initiating allopurinol, a xanthine oxidase inhibitor, vs benzbromarone, a uricosuric. Methods Using the 2011–2020 Korea National Health Insurance Service database, we conducted a cohort study on gout patients initiating allopurinol vs benzbromarone as the 1st-line urate-lowering treatment (ULT). The primary outcome was a new onset urinary stone. The secondary outcome was a stone requiring intervention. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazard models with a 5:1 ratio propensity-score matching on > 80 variables. Subgroup analyses were done by age, sex, thiazide use, and cardiovascular (CV) risk. Results 61 300 allopurinol initiators PS-matched on 12 260 benzbromarone initiators were included (mean age 59 years, 79% male). During a mean follow-up of 322 days, 619 urolithiasis cases occurred with an incidence rate of 0.87 per 100 person-years in allopurinol and 1.39 in benzbromarone initiators, showing a HR of 0.64 (95% CI, 0.51–0.80). ∼44% of urinary stones required intervention with a HR of 0.61 (95% CI 0.43–0.88). The lower risk associated with allopurinol compared with benzbromarone persisted across subgroups but was greater in the high than non-high CV risk subgroup (p for interaction = 0.02) Conclusion This population-based cohort study found that allopurinol compared with benzbromarone was associated with a substantially lower risk of urolithiasis particularly in the presence of the high CV risk. This finding provides important safety information for clinicians’ decision-making on ULTs of different mechanisms of action.

中文翻译：

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痛风患者中别嘌呤醇与苯溴马隆相关的尿石症风险：一项基于人群的队列研究

目的 比较痛风患者开始使用别嘌呤醇（一种黄嘌呤氧化酶抑制剂）与苯溴马隆（一种促尿酸排泄药）的尿石症风险。方法 利用 2011-2020 年韩国国民健康保险服务数据库，我们对开始别嘌呤醇与苯溴马隆作为第一线降尿酸治疗 (ULT) 的痛风患者进行了队列研究。主要结局是新发尿路结石。次要结果是需要干预的结石。我们使用 Cox 比例风险模型估计了风险比 (HR) 和 95% 置信区间 (CI)，其中 5:1 比例的倾向得分匹配大于 1。 80 个变量。按年龄、性别、噻嗪类药物使用和心血管 (CV) 风险进行亚组分析。结果 包括 61 300 个别嘌呤醇引发剂与 12 260 个苯溴马隆引发剂 PS 匹配（平均年龄 59 岁，79% 男性）。在平均 322 天的随访期间，发生了 619 例尿石症病例，别嘌呤醇组的发病率为每 100 人年 0.87 例，苯溴马隆引发剂组为 1.39 例，HR 为 0.64（95% CI，0.51-0.80）。 ∼44% 的尿路结石需要干预，HR 为 0.61 (95% CI 0.43–0.88)。与苯溴马隆相比，别嘌呤醇的相关风险较低在各个亚组中持续存在，但在高心血管风险亚组中高于非高心血管风险亚组（交互作用 p = 0.02） 结论 这项基于人群的队列研究发现，与苯溴马隆相比，别嘌呤醇与降低尿石症的风险，特别是在存在高心血管风险的情况下。这一发现为临床医生对不同作用机制的 ULT 决策提供了重要的安全信息。