University of Alabama at Birmingham.
University of Chicago Pritzker School of Medicine, Chicago, Illinois.
Arthritis Rheumatol. 2022 Sep;74(9):1593-1601. doi: 10.1002/art.42160. Epub 2022 Aug 5.
To investigate whether serum urate levels, number of gout flares, and tophi burden are related to death from cardiovascular (CV) causes after treatment with febuxostat or allopurinol in patients with gout from the Cardiovascular Safety of Febuxostat or Allopurinol in Patients With Gout and Cardiovascular Comorbidities (CARES) trial.
Patients were randomly assigned to receive febuxostat (40 mg or 80 mg once daily, according to serum urate levels at week 2) or allopurinol titrated in 100-mg increments from 200-400 mg or 300-600 mg (with dose determined according to kidney function). Changes from baseline in serum urate level, gout flares, and tophus resolution were key exploratory efficacy parameters in the overall population and in subgroups of patients who died and those who did not die from a CV-related cause. The latter subgroup included patients who died due to non-CV causes and those who did not die due to any cause.
Patients received treatment with febuxostat (n = 3,098) or allopurinol (n = 3,092) for a median follow-up period of 32 months (for a maximum of 85 months). In the overall population, mean serum urate levels were lower in those receiving febuxostat compared with those receiving allopurinol at most study visits. There were no associations between serum urate levels and death from CV causes with febuxostat. The number of gout flares requiring treatment was higher within 1 year of treatment with febuxostat compared with allopurinol (mean incidence of gout flares per patient-years of exposure 1.33 versus 1.20), but was comparable thereafter and decreased overall throughout the study period (mean incidence of gout flares per patient-years of exposure 0.35 versus 0.34 after 1 year of treatment; overall mean incidence 0.68 versus 0.63) irrespective of whether the patient died from a CV-related cause. Overall, 20.8% of patients had ≥1 tophus at baseline; tophus resolution rates were similar between treatment groups, with cumulative resolution rates of >50%.
In the CARES trial, febuxostat and allopurinol (≤600 mg doses) had comparable efficacy in patients with gout and CV disease, and there was no evidence of a relationship between death from CV causes and serum urate levels, number of gout flares, or tophus resolution among the patients receiving febuxostat.
在心血管安全性的别嘌呤醇或非布司他在痛风和心血管合并症患者（CARES）试验中，研究接受别嘌呤醇或非布司他治疗的痛风患者的血清尿酸水平、痛风发作次数和痛风石负担与心血管（CV）死因死亡之间的关系。
患者随机分配接受非布司他（40mg 或 80mg 每日一次，根据第 2 周的血清尿酸水平）或别嘌呤醇（从 200-400mg 或 300-600mg 开始逐步增加 100mg，根据肾功能而定）治疗。血清尿酸水平、痛风发作和痛风石溶解的变化是总体人群和死亡和非 CV 相关原因死亡的患者亚组的关键探索性疗效参数。后者亚组包括因非 CV 原因死亡的患者和因任何原因未死亡的患者。
患者接受非布司他（n=3098）或别嘌呤醇（n=3092）治疗的中位随访时间为 32 个月（最长 85 个月）。在总体人群中，接受非布司他治疗的患者的平均血清尿酸水平低于接受别嘌呤醇治疗的患者，在大多数研究访视中。在接受非布司他治疗的患者中，血清尿酸水平与 CV 死因死亡之间没有关联。与别嘌呤醇相比，接受非布司他治疗的患者在治疗的 1 年内需要治疗的痛风发作次数更高（每个患者每年暴露的痛风发作发生率为 1.33 与 1.20），但此后相当，并且在整个研究期间总体减少（治疗 1 年后每个患者每年暴露的痛风发作发生率为 0.35 与 0.34；总体平均发生率为 0.68 与 0.63），无论患者是否因 CV 相关原因死亡。总体而言，20.8%的患者基线时有≥1 个痛风石；治疗组之间的痛风石溶解率相似，累积溶解率>50%。
在 CARES 试验中，非布司他和别嘌呤醇（≤600mg 剂量）在痛风合并 CV 疾病的患者中具有相当的疗效，在接受非布司他治疗的患者中，没有证据表明 CV 死因死亡与血清尿酸水平、痛风发作次数或痛风石溶解之间存在关系。
