西洛他唑与阿司匹林对缺血性脑卒中二级预防的系统评价

Efficacy and Safety in Secondary Prevention of Ischemic Stroke with Cilostazol or Aspirin:A Systematic Review

目的系统评价西洛他唑对比阿司匹林在缺血性脑卒中二级预防中的有效性与安全性。方法计算机检索Cochrane图书馆(2009年4期)、PubMed(1980.1～2009.11),EMBASE(1980.1～2009.11)、中国生物医学文献数据库(1978.1～2009.11)、CNKI(1979.1～2009.11)等数据库,收集所有西洛他唑对比阿司匹林治疗缺血性脑卒中的随机对照试验(RCT)和交叉试验,提取数据,依据Cochrane Handbook 5.0.2推荐的方法评价纳入研究质量,采用RevMan5.0软件进行统计学分析。结果研究纳入2个随机对照试验和1个交叉对照试验,共838位受试者。其中1篇随机对照试验质量较高,1篇随机对照试验和交叉对照试验质量较低。Meta分析结果显示,西洛他唑组在治疗缺血性脑卒中患者的初期结果(30d[RR=3.00,95%CI(0.31,28.70)]、90d[RR=1.67,95%CI(0.40,6.92)]、180d[RR=1.25,95%CI(0.50,3.13)]、360d[RR=0.65,95%CI(0.33,1.29)]、540d[RR=0.80,95%CI(0.54,1.18)]);二期结果(30d[RR=4.00,95%CI(0.45,35.61)]、90d[RR=1.75,95%CI(0.52,5.93)]、180d[RR=1.00,95%CI(0.48,2.07)]、360d[RR=0.77,95%CI(0.45,1.29)]、540d[RR=0.66,95%CI(0.40,1.09)]);卒中复发率:西洛他唑组:RR=0.64,95%CI(0.31,1.30),阿司匹林组:RR=0.21,95%CI(0.04,1.06);血液中血小板衍生物水平(PDMP)[RR=1.00,95%CI(0.39,2.58)]方面与阿司匹林组差异无统计学意义。但西洛他唑组在颅内出血率[RR=7.14,95%CI(0.7,58.33)]等安全性指标的发生率低于阿司匹林组。结论西洛他唑与阿司匹林在缺血性脑卒中的二级预防方面疗效相似,且服用西洛他唑发生头晕、头痛、心动过速和心悸的概率高于服用阿司匹林,但服用西洛他唑颅内出血率和其他脏器出血率方面低于服用阿司匹林。由于部分纳入研究质量级别较低,所以两种药物对缺血性脑卒中的二级预防的治疗有待实施高质量大样本临床试验进一步验证。

Objective To review the efficacy and safety in secondary prevention of ischemic stroke with cilostazol or aspirin.Methods we searched Cochrane Library（the 4th issue,2009 ）,PubMed（1980.1～2009.11）,EMBASE（1980.1～2009.11）,CBM（1978.1～2009.11）,CNKI（1979.1～2009.11） and some other databases,then collected all of the studies describing the outcomes in curing the ischemic stroke after taking cilostazol or aspirin. According to the strict inclusion and exclusion criteria,two reviewers independently selected trials,extracted datas,made cross-checking and methodological quality assessment of the homogeneity studies by using the Cochrane systematic review methods,then made Meta analysis using RevMan 5.0 software.Results This systematic review study included two randomized controlled trials and a cross-over trial,which contained a total of 838 participants. The evidence quality of one of the randomized controlled trials was high,however,the evidence quality of another randomized controlled trial and the cross-over trial was poor. Meta analysis results suggested that the effectiveness of cilostazol and aspirin in the secondary prevention of ischemic stroke performed no significantly statistical difference：primary endpoint（30 d[RR=3.00,95%CI（0.31,28.70）]; 90 d[RR=1.67,95%CI（0.40,6.92）]; 180 d[RR=1.25,95%CI（0.50,3.13）]; 360 d[RR=0.65,95%CI（0.33,1.29）]; 540 d[RR=0.80,95%CI（0.54,1.18）]）; combined endpoint（30 d[RR=4.00,95%CI（0.45,35.61）]; 90 d [RR=1.75,95%CI（0.52,5.93）]; 180 d[RR=1.00,95%CI（0.48,2.07）]; 360 d [RR=0.77,95%CI（0.45,1.29）]; 540 d[RR=0.66,95%CI（0.40,1.09）]）; the recurrence of ischemic stroke：cilostazol group：RR=0.64,95%CI（0.31,1.30）,aspirin group：RR=0.21,95%CI（0.04,1.06）; PDMP[RR=1.00,95%CI（0.39,2.58）]. But in terms of the probability of intracranial hemorrhage （[RR=7.14,95%CI（0.7,58.33）]） and other safety standards,taking cilostazol performed lower than taking aspirin.Conclusion The side effects of cilostazol and aspirin in the treatment for ischemic stroke were similar to each other,but in terms of the probability of dizziness,headache,tachycardia and palpitation,taking cilostazol performed higher than taking aspirin,however,taking cilostazol performed lower in the probability of intracranial hemorrhage and other organ hemorrhage than taking aspirin. Since this study included a small amount of studies,in which the evidence quality of one of the randomized controlled trials and the cross-over study was poor,therefore,it would be necessary to make a further validation with lots of high-quality clinical trials.