【作者】 平燕婷；

【导师】 戴海斌；

【作者基本信息】 浙江大学 ， 药学， 2015， 硕士

【摘要】 目的：评估脑卒中患者根据Essen卒中风险评分(Essen Stroke Risk Score,ESRS)来选择二级预防药物抗血小板药的合理性；研究不同Essen风险评分下,非心源性脑卒中患者抗血小板药物治疗的有效性和安全性。方法：本研究回顾性收集2009年1月-2011年12月间连续收入浙江大学医学院附属第二医院神经内科病房的所有非心源性缺血性脑卒中患者作为研究对象,调查临床资料,采用电话随访患者本人或家属,2015年9月完成随访工作,随访时间最长6.7年,最短3.7年,随访平均时间5.2年。随访记录患者出院后抗血小板药的种类、使用率、发生血管终点事件(血管性死亡、卒中、心肌梗死)、神经功能改善情况(改良RANKIN量表mRS评分)以及安全性(胃肠道反应、出血)等情况。根据患者出院时抗血小板药物使用种类,分为阿司匹林组和氯吡格雷组,对每组进一步按Essen卒中风险评分分类,分为Essen<3、Essen=3、Essen>3三类,对不同组别的疗效与不良反应进行分析。结果：1本研究纳入的非心源性缺血性脑卒中患者的总病例数1175例,失访病例数297例,最终有效随访病例数878例,失访率为25.28%。2脑卒中患者发生血管终点事件的情况：当ESRS<3时,阿司匹林组血管终点事件发生率略高于氯吡格雷组(10.60%：7.41%,P=0.600),但差异无统计学意义；当ESRS=3时,氯吡格雷组血管终点事件发生率明显高于阿司匹林组(24.00%：12.57%,P=0.025);当ESRS>3时,阿司匹林组血管终点事件发生率明显高于氯吡格雷组(27.39%：14.84%,P=0.003)。3脑卒中患者神经功能(改良RANKIN量表mRS评分)改善情况：当ESRS<3时,阿司匹林组与氯吡格雷组的mRS评分差值无差异(0.31±1.63：0.38±1.75,P=0.457)；当ESRS=3时,氯吡格雷组的mRS评分差值大于阿司匹林组(0.35±1.79：0.09±1.70,P=0.216),但差异无统计学意义；当ESRS>3时,氯吡格雷组的mRS评分差值明显大于阿司匹林组(0.07±1.79：-0.32±1.88,P=0.003)。4脑卒中患者阿司匹林或氯吡格雷的使用率：当ESRS<3时,氯吡格雷组停药率明显高于阿司匹林组(51.85%：25.83%,P=0.006)；当ESRS=3时,氯吡格雷组停药率高于阿司匹林组(28.00%：16.77%,P=0.044)；当ESRS>3时,阿司匹林组与氯吡格雷组停药率无显著性差异(13.20%：14.84%,P=0.630)。进一步研究停药原因,由于不良反应停药,阿司匹林组明显高于氯吡格雷组(57.94%：32.76%,P=0.002)；由于未复诊或自行停药,氯吡格雷组明显高于阿司匹林组(44.83%：27.10%,P=0.021)。对停药发生的时间进行分析,出院1年内停药,氯吡格雷组明显高于阿司匹林组(50.55%：28.04%,P=0.005)；出院4-5年后停药,阿司匹林组明显高于氯吡格雷组(35.51%：12.07%,P=0.001)。5脑卒中患者使用阿司匹林或氯吡格雷的安全性：在ESRS<3中,阿司匹林组不良反应发生率高于氯吡格雷组(13.25%：7.41%,P=0.369),但无统计学差异；在ESRS=3中,阿司匹林组不良反应发生率高于氯吡格雷组(12.57%：8.00%,P=0.296),但差异无统计学意义；在ESRS>3中,阿司匹林组与氯吡格雷组不良反应发生率无差异(6.93%：7.10%,P=0.947)。6多因素变量分析,在ESRS<3中,抗血小板药物停药率[OR=3.471,95%CI (1.222,9.859), P=0.019]为脑卒中复发的独立因素；在ESRS=3中,抗血小板药物选择阿司匹林较氯吡格雷[OR=0.432,95%CI(0.229,0.814),P=0.009]和抗血小板药物停药率[OR=2.063,95%CI(1.103,3.859), P=0.023]为脑卒中复发的独立因素；在ESRS>3中,抗血小板药物选择阿司匹林较氯吡格雷[OR=2.035, 95%CI(1.208,3.430), P=0.008]和抗血小板药物停药率[OR=2.415,95%CI (1.119,5.214), P=0.025]为脑卒中复发的独立因素。结论：1.当ESRS<3时,阿司匹林组停药率明显低于氯吡格雷组,且两药在血管终点事件发生率、神经功能改善情况、安全性方面均无差异,因此选择阿司匹林用于脑卒中二级预防较氯吡格雷更合适。2.当ESRS=3时,阿司匹林组血管终点事件发生率明显低于氯吡格雷组、停药率明显低于氯吡格雷组,且两药在神经功能改善情况和安全性方面均无差异,因此选择阿司匹林用于脑卒中二级预防较氯吡格雷更合适。3.当ESRS>3时,氯吡格雷组血管终点事件发生率明显低于阿司匹林组、神经功能改善情况明显优于阿司匹林组、且两药的使用率和安全性方面均无差异,因此选择氯吡格雷用于脑卒中二级预防较阿司匹林更合适。更多还原

【Abstract】 Objective:To evaluate antiplatelet drugs on secondary prevention of stroke with Essen Stroke Risk Score (Essen Stroke Risk Score, ESRS); and investigate efficacy and safety of antiplatelet drugs in non-cardiogenic stroke patients under different Essen score.Methods:This research was retrospectively, continuously carried on the Neurology wards of Zhejiang University Second Affiliated Hospital, and all non-cardiac ischemic stroke patients were enrolled to investigate from January 2009 to December 2011. Telephone follow-up to patients or their families was finished in September 2015. The longest follow-up time was 6.7 years and the shortest’s was 3.7 years; the average follow-up time was 5.2 years. The kind of antiplatelet drugs used after dischareing, the usage rate of antiplatelet drugs, the incidence of vascular endpoint event (vascular death, stroke, myocardial infarction), the improvement of neurological function (modified RANKIN scale mRS score),the security of antiplatelet drugs(gastrointestinal reactions, bleeding)were recerded in the follow-up. According to the kind of antiplatelet drugs used after discharged, the patients were divided into Group aspirin and Group clopidogrel. According to Essen Stroke Risk Score, each group was further divided into three groups:Essen<3, Essen=3 and Essen>3. The efficacy and the adverse reactions of each group was analyzed.Results:1 There are 1175 non-cardiac ischemic stroke patients were enrolled in this research was,297 cases were lost in the follow-up, and the final effective cases was 878; the missing visit rate was 25.28 percent.2 About the endpoint of vascular stroke:when ESRS<3, Group aspirin was slightly higher than that of Group clopidogrel (10.60%:7.41%, P= 0.600), but there is no statistical difference between these groups; when ESRS= 3, Group clopidogrel was significantly higher than that of Group aspirin (24.00%:12.57%, P= 0.025); when ESRS> 3, Group aspirin was significantly higher than that of Group clopidogrel (27.39%:14.84%, P= 0.003).3 About neurological function (modified RANKIN scale mRS score) improved: when ESRS<3, there was no difference of mRS score improving between Group aspirin and Group clopidogrel (0.31±1.63:0.38±1.75, P=0.457); when ESRS=3, the mRS score decreasing of Group clopidogrel is greater than that of Group aspirin (0.35±1.79: 0.09±1.70, P=0.216), but there is no statistical difference between of them; when ESRS> 3, the mRS score decreasing of Group clopidogrel was significantly higher than that of Group aspirin (0.07±1.79:-0.32±1.88, P=0.003).4 About the usage rate of aspirin or clopidogrel in stroke patients:when ESRS<3, the discontinuation rate of Group clopidogrel was significantly higher than that of Group aspirin (51.85%:25.83%, P= 0.006); when ESRS= 3, the discontinuation rate of Group clopidogrel was higher than that of Group aspirin (28.00%:16.77%, P= 0.044); when ESRS> 3, there is no significant difference between the discontinuation rate of Group aspirin and Group clopidogrel (13.20%:14.84%, P= 0.630). Further explored of discontinuation reasons of adverse events, Group aspirin was significantly higher than that of Group clopidogrel (57.94%:32.76%, P= 0.002); being of no referral or self-withdrawal, the discontinuation reasons of Group clopidogrel was significantly higher than that of Group aspirin (44.83%:27.10%, P= 0.021). Further to analyze the drug withdrawal time, when it happened in 1 year, Group clopidogrel was significantly higher than that of Group aspirin (50.55%:28.04%, P= 0.005); when happened in 4-5 years, Group aspirin was significantly higher than that of Group clopidogrel (35.51%: 12.07%, P= 0.001).5 About the safety of aspirin or clopidogrel used stroke patients:when ESRS<3, the adverse reactions rates of Group aspirin was higher than that Group clopidogrel (13.25%:7.41%, P= 0.369),but there is no statistical difference between of them;when ESRS= 3, the adverse reactions rates of Group aspirin was higher than that of Group clopidogrel (12.57%:8.00%, P= 0.296), but there is no statistical difference between of them; when ESRS> 3, there was no difference of adverse reactions rates between Group aspirin and Group clopidogrel (6.93%:7.10%, P= 0.947).6 To further explore multivariate variables analysis:when ESRS<3, the drug withdrawal rate of antiplatelet drugs [OR= 3.471,95% CI (1.222,9.859), P= 0.019] was the independent factor of stroke recurrence; when ESRS= 3, the antiplatelet drug selection of aspirin or clopidogrel [OR= 0.432,95% CI (0.229,0.814), P= 0.009] and the drug withdrawal rate of antiplatelet drugs [OR= 2.063,95% CI (1.103,3.859), P= 0.023] were the independent factors of stroke recurrence; when ESRS> 3, the antiplatelet drug selection of aspirin or clopidogrel [OR= 2.035,95% CI (1.208,3.430), P= 0.008] and the drug withdrawal rate of antiplatelet drugs [OR= 2.415,95% CI (1.119,5.214), P= 0.025] were the independent factors of stroke recurrence.Conclusions:1 When ESRS<3, the drug withdrawal rate of Group aspirin was significantly lower than that of Group clopidogrel, but there is no difference in the vascular endpoint event, neurological function improving, safety between in these two groups. Thus, choosing aspirin for secondary prevention of stroke compared is more appropriate to clopidogrel.2 When ESRS= 3, the vascular endpoint event of Group aspirin was significantly lower than that of Group clopidogrel, the drug withdrawl rate of Group aspirin was significantly lower than that of Group clopidogrel, but there were no difference neurological function improving and the safety between of them, Thus, choosing aspirin for secondary prevention of stroke is more appropriate to clopidogrel.3 When ESRS> 3, the incidence of vascular endpoint event of Group clopidogrel was significantly lower than that of Group aspirin, and the neurological function improving was significantly better than that of Group aspirin, but there is no difference of the usage rate and the safety between of these two drugs, Thus, choosing clopidogrel for secondary prevention of stroke is more appropriate than aspirin.更多还原