非布司他心血管安全性新解读

A new interpretation of the cardiovascular safety of febuxostat

非布司他是一种口服的非嘌呤选择性黄嘌呤氧化酶抑制剂,2008年首先在欧洲被批准用于治疗痛风患者的慢性高尿酸血症,2009年被美国FDA批准用于治疗痛风。2013年,有研究者发现非布司他与心血管血栓栓塞事件可能存在相关性。2017年,美国FDA发布非布司他安全警示。2018年3月,历时8年的“合并心血管疾病痛风患者使用非布司他和别嘌醇心血管安全性”(CARES)研究结果正式发表,该研究显示合并心血管疾病的痛风患者使用非布司他会增加全因死亡风险和心血管死亡风险。但随后开展的多项非布司他相关临床研究结果显示,非布司他并未增加心血管风险和心血管死亡风险,反而可能对高尿酸血症患者具有心脑血管和肾脏保护作用。目前非布司他心血管安全性的研究总体来说结论并不明确,需要进行更多的临床研究综合分析,尤其是对于中国人群的研究。在考虑使用非布司他进行治疗之前,需仔细询问患者是否存在相关心血管疾病病史,以及是否有非甾体类抗炎药、抗血小板药等合并用药情况,在充分考虑可能风险后谨慎选择使用。

Febuxostat, an oral non-purine selective xanthine oxidase inhibitor, was approved firstly in Europe in 2008 for the treatment of chronic hyperuricemia in gout patients, and then in 2009 for the treatment of gout by the US FDA. In 2013, it was found by researchers that there was a possible correlation between febuxostat and cardiovascular thromboembolism events. In 2017, the US FDA issued a safety warning for febuxostat. In March 2018, the results of an eight-year study on Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Comorbidities(CARES)was officially published. The study showed that febuxostat increased all-cause mortality and cardiovascular mortality in gout patients with cardiovascular disease. However, in subsequent clinical studies related to febuxostat, it was concluded that febuxostat did not increase cardiovascular risk and mortality, and could have cardio-cerebrovascular and renal protective effects in patients with hyperuricemia. Currently, the pros and cons of febuxostat on cardiovascular safety are not clear in general studies, and more clinical studies are needed, especially in the Chinese population. Thus, before treatment with febuxostat, it is necessary to carefully inquire whether the patient has a history of cardiovascular diseases, and whether there is a combination use of NSAID, antiplatelet drugs and so on. Febuxostat should be used only after a full consideration of the possible risks.