替格瑞洛对比氯吡格雷治疗携带CYP2C19功能缺失等位基因的轻度缺血性卒中或短暂性脑缺血发作患者有效性和安全性的系统评价

Systematic Review of the Efficacy and Safety of Ticagrelor Versus Clopidogrel in CYP2C19 Loss-of-function Carriers with Mild Ischemic Stroke or Transient Ischemic Attack

关键词:  CYP2C19  功能缺失等位基因  轻度缺血性卒中  短暂性脑缺血发作  替格瑞洛  氯吡格雷  有效性  安全性

Key words:  CYP2C19  loss-of-function allele  mild ischemic stroke  transient ischemic attack  ticagrelor  clopidogrel  efficacy  safety

摘要:

目的 系统评价替格瑞洛对比氯吡格雷治疗携带细胞色素P450 2C19(cytochrome P450 2C19，CYP2C19)功能缺失等位基因的轻度缺血性卒中或短暂性脑缺血发作(transient ischemic attack，TIA)患者的有效性和安全性。方法 系统检索PubMed、Embase、the Cochrane Library、中国知网(CNKI)、万方等数据库，检索时限均为建库至2022年6月。由2名研究者独立筛选文献、提取资料并评价纳入研究的方法学质量，使用RevMan 5.3软件进行meta分析。结果 共纳入2篇研究，7 087例患者。与氯吡格雷比较，替格瑞洛降低携带CYP2C19 功能缺失等位基因的轻度缺血性卒中或TIA患者卒中[RR=0.78，95%CI(0.66~0.93)，I²=0%，P=0.007]和血管事件[RR=0.78，95%CI(0.66~0.91)，I²=0%，P=0.002]发生率。替格瑞洛-阿司匹林组任何出血[HR=2.18，95%CI(1.66~2.85)]和小出血[HR=2.41，95%CI(1.81~3.20)]发生率高于氯吡格雷-阿司匹林组，且替格瑞洛-阿司匹林组呼吸困难(1.2% vs 0.2%，P<0.001)和心律失常(1.7% vs 0.8%，P=0.001)比氯吡格雷-阿司匹林组更常见；2组严重出血发生率差异无统计学意义。结论 与氯吡格雷比较，替格瑞洛降低携带CYP2C19 功能缺失等位基因的轻度缺血性卒中或TIA患者卒中和血管事件发生率，且不增加严重出血风险；但替格瑞洛组小出血、呼吸困难和心律失常发生率高。

Abstract:

OBJECTIVE To systematically review the efficacy and safety of ticagrelor versus clopidogrel in CYP2C19 loss-of-function carriers with mild ischemic stroke or transient ischemic attack(TIA). METHODS Databases such as PubMed, Embase, the Cochrane Library, CNKI, and Wanfang were systematically searched, and the search period was from database establishment to June 2022. Two reviewers independently screened literature, extracted data, and evaluated the methodological quality of the included studies. Meta-analysis was performed using RevMan 5.3 software. RESULTS A total of 2 studies with 7 087 patients were included. Compared with clopidogrel, ticagrelor reduced the incidence of stroke[RR=0.78, 95%CI(0.66-0.93), I²=0%, P=0.007] and vascular event[RR=0.78, 95%CI(0.66-0.91), I²=0%, P=0.002] in patients with mild ischemic stroke or TIA carrying the CYP2C19 loss-of-function allele. The incidence of any bleeding[HR=2.18, 95%CI(1.66-2.85)] and minor bleeding[HR=2.41, 95%CI (1.81-3.20)] in the ticagrelor-aspirin group was higher than that in the clopidogrel-aspirin group, and dyspnea (1.2% vs 0.2%, P<0.001) and arrhythmias(1.7% vs 0.8%, P=0.001) were more common in the ticagrelor-aspirin group than in the clopidogrel-aspirin group. There was no significant difference in the incidence of severe bleeding between the two groups. CONCLUSION Compared with clopidogrel, ticagrelor reduces the incidence of stroke and vascular events in patients with mild ischemic stroke or TIA carrying the CYP2C19 loss-of-function allele, and did not increase the risk of severe bleeding. However, the ticagrelor group had a higher incidence of minor bleeding, dyspnea and arrhythmias.