非布司他对比别嘌醇治疗痛风患者心血管不良事件及死亡风险的Meta分析

目的： 对非布司他相比别嘌醇用于治疗痛风患者的心血管不良事件及死亡风险做Meta分析。方法： 计算机检索PubMed、EMbase、Cochrane Library（2020年第1期）、CNKI、CBM、VIP、Wanfang数据库，搜集非布司他对比别嘌醇用于治疗痛风患者的随机对照试验（RCT），检索时限均从建库至2020年1月。由2名研究者独立进行文献筛选与提取资料工作，并对纳入研究的偏倚风险进行评价后，采用RevMan5.3软件对纳入研究进行Meta分析。结果： 共纳入11个RCT，包含12 492例患者。Meta分析结果显示：2种方案心血管不良事件的发生率并无显著性差异OR=1.09，95% CI（0.94，1.27），P=0.24]，但随着非布司他日剂量的增加，发生心血管不良事件的风险也就越大；非布司他相比别嘌醇，心血管死亡及任意原因引起的死亡的风险更高OR=1.32，95% CI（1.02，1.72），P=0.03]、OR=1.24，95% CI（1.02，1.50），P=0.03]，亚组分析中，对于痛风合并心血管疾病的患者，非布司他的心血管死亡以及任意原因引起的死亡风险高于别嘌醇OR=1.35，95% CI（1.04，1.76），P=0.02]、OR=1.24，95% CI（1.02，1.50），P=0.03]，对于痛风不仅限于合并心血管疾病的患者，非布司他与别嘌醇相比，其导致的心血管死亡与任意原因引起的死亡的风险并无显著区别OR=0.77，95% CI（0.21，2.85），P=0.69]OR=1.29，95% CI（0.41，4.05），P=0.66]。结论： 当前证据显示，不论痛风患者是否合并有心血管疾病，其心血管不良事件的发生风险都可能随着非布司他日剂量的增加而升高；死亡风险（心血管相关死亡及任意原因引起的死亡）方面，对于痛风合并心血管疾病患者，非布司他的风险高于别嘌醇，而对于痛风不仅限于合并心血管疾病的患者，2种药物所引起的死亡风险并没有差别。但是考虑到纳入研究的质量和数量限制，上述结论仍需要更多的新的高质量研究进行验证。

Cardiovascular safety and mortality of febuxostat versus allopurinol in patients with gout:Meta-analysis

OBJECTIVE To compare the cardiovascular safety and mortality of febuxostat versus allopurinol in patients with gout. METHODS PubMed,EMbase,Cochrane Library(Issue 1 of 12,January 2020),CNKI,CBM,VIP and Wanfang databases were electronically searched for retrieving RCTs on febuxostat versus allopurinol in patients with gout from inception to January,2020.Two reviewers independently screened the literature,extracted the relevant data and assessed the risk of bias of included studies.Then meta-analysis was performed by RevMan 5.3 software.RESULTS A total of 11 RCTs involving 12 492 patients were included.The results of meta-analysis revealed no significant inter-group difference in risk of adverse cardiovascular events OR=1.09,95%CI(0.94,1.27),P=0.24].However,the risk of adverse cardiovascular events increased with a higher dose of febuxostat;febuxostat has higher cardiovascular and all-cause mortality versus allopurinol in patients with gout OR=1.32,95%CI(1.02,1.72),P=0.03]OR=1.24,95%CI(1.02,1.50),P=0.03],in subgroup analysis,febuxostat had higher cardiovascular and all-cause mortality for patients with gout and cardiovascular diseases OR=1.35,95%CI(1.04,1.76),P=0.02]OR=1.24,95%CI(1.02,1.50),P=0.03].For patients with gout and complications non-limited in cardiovascular diseases,there were no significant inter-group differences in cardiovascular and all-cause mortalities OR=0.77,95%CI(0.21,2.85),P=0.69]OR=1.29,95%CI(0.41,4.05),P=0.66].CONCLUSION Regardless of with or without cardiovascular complications,the risk of adverse cardiovascular events probably increases with a higher dose of febuxostat for patients with gout.For patients with gout and cardiovascular diseases,mortality(cardiovascular and all-cause)is higher with febuxostat than with allopurinol.However,for patients with gout and complications non-limited in cardiovascular diseases,no significant difference in mortality exists between two drugs Due to limited quality and quantity of included studies,more high-quality studies are required for confirming the above conclusions.