氯吡格雷联合阿司匹林在TIA治疗和二级预防中的应用观察

目的 探讨氯吡格雷联合阿司匹林在短暂性脑缺血发作(TIA)治疗和二级预防中的有效性和安全性.方法 将252例TIA患者随机分成阿司匹林组、氯吡格雷组和联合组(阿司匹林+氯吡格雷),通过治疗前后血小板活化指标短暂性脑缺血发作(TIA)或脑梗死发生率以及出血等不良反应的比较,判断氯吡格雷联合阿司匹林在TIA治疗和二级预防中的有效性和安全性.结果 3组病例治疗前后血小板活化指标、TIA再发率及脑梗死发生率统计显示,氯吡格雷组优于阿司匹林组(P＜0.05),联合组优于氯吡格雷组(P＜0.05);随访6个月时,出血等不良反应3组无明显差异;12个月时,联合组出血风险增加(P＜0.05).结论 氯吡格雷联合阿司匹林在TIA治疗和二级预防中效果确切,优于两种药物单用.短时期内联用出血风险未增加,而长期应用时,有可能增加出血风险.     

不同剂量阿托伐他汀联合氯吡格雷治疗短暂性脑缺血发作的疗效及对预后的影响

目的探讨不同剂量阿托伐他汀联合氯吡格雷治疗短暂性脑缺血发作(TIA)的疗效及对预后的影响。方法66例TIA患者随机分为2组,对照组予阿托伐他汀(20mg/d)联合氯吡格雷治疗,观察组予高剂量阿托伐他汀(40mg/d)联合氯吡格雷治疗,比较2组近期疗效及随访12个月TIA复发次数、脑梗死发生率。结果 2组总有效率比较差异无统计学意义(P0.05),但观察组基本痊愈率(75.76%)显著高于对照组(51.52%),差异有统计学意义(P0.05);随访12个月观察组TIA复发次数明显少于对照组,脑梗死发生率也低于对照组,差异均有统计学意义(P0.05)。结论高剂量阿托伐他汀(40mg/d)联合氯吡格雷治疗TIA可快速有效控制临床症状,减少复发并阻止TIA的进一步发展。     

两种方案治疗TIA疗效分析

目的观察负荷剂量氯吡格雷联合阿司匹林及单用阿司匹林治疗短暂性脑缺血发作(TIA)的临床疗效及安全性。方法选取110例确诊为非心源性TIA的患者,随机分为观察组与对照组。对照组55例,予以肠溶阿司匹林治疗;观察组55例,在对照组治疗基础上,增加氯吡格雷治疗。治疗1个月后对2组疗效进行对比观察,并随访6个月以观察其安全性。结果观察组患者总有效率92.73%,对照组患者总有效率76.36%,2组差异有统计学意义(P<0.05)。6个月内2组患者均未出现消化道、牙龈、皮肤黏膜出血和脑梗死等。结论 TIA后,与单用阿司匹林相比,负荷量氯吡格雷联合应用阿司匹林在合理风险的范围内可取得更好的临床疗效,值得借鉴。     

氯吡格雷联合阿司匹林治疗短暂性脑缺血发作的疗效观察

目的探讨氯吡格雷联合阿司匹林治疗短暂性脑缺血发作(TIA)的效果及安全性。方法选取2012-01-2016-01在中信中心医院内科治疗的116例TIA患者,随机分为对照组和观察组各58例。2组均给予降糖、降压等常规治疗,对照组在此基础上口服阿司匹林;观察组在常规治疗基础上给予氯吡格雷和阿司匹林,2组均连续服用4周,比较治疗前后2组血液流变学指标及不良反应情况,并随访6个月观察2组治疗有效率。结果观察组治疗有效率为96.55%明显高于对照组84.48%(P0.05);治疗后,2组血液流变学指标均较治疗前明显改善(P0.05),观察组全血黏度低切、全血黏度高切、血浆黏度及纤维蛋白含量均明显低于对照组(P0.05);观察组脑梗死发生率1.72%明显,低于对照组12.07%(P0.05),观察组不良反应率5.17%,与对照组6.90%比较无明显差异(P0.05)。结论氯吡格雷联合阿司匹林治疗短暂性脑缺血发作患者能够有效改善患者的血流指标,降低脑梗死发生率,效果显著且安全可行。     

氯吡格雷联合阿司匹林与低分子肝素联合阿司匹林治疗短暂性脑缺血发作近期疗效观察

目的探讨氯吡格雷联合阿司匹林与低分子肝素联合阿司匹林治疗短暂性脑缺血发作(transient ischemic attack,TIA)的疗效。方法收集入院治疗的102例TIA患者,按ABCD3-I评分法分为低(4)、中高危(≥4)2组,每组再随机分为双抗(氯吡格雷+阿司匹林)组和抗凝(低分子肝素+阿司匹林)组。观察7d内2组TIA控制率,记录不良反应,随访1个月。结果低危组的双抗组有效率(97.6%)略高于抗凝组(95.1%,P=0.556);中高危组的抗凝组有效率(90.0%)高于双抗组(80.0%),差异无统计学意义(P0.05)。双抗组不良反应均低于抗凝组,差异无统计学意义(P0.05)。结论对ABCD3-I评分≤4的低危患者优先选择氯吡格雷联合阿司匹林治疗,对ABCD3-I评分≥4的中高危患者,低分子肝素联合阿司匹林的近期疗效可能优于氯吡格雷联合阿司匹林。     

阿托伐他汀钙联合氯吡格雷治疗短暂性脑缺血发作疗效观察

目的观察阿托伐他汀联合氯吡格雷治疗短暂性脑缺血发作(TIA)的有效性和安全性。方法选择TIA患者80例,随机分为治疗组、对照组各40例,2组基础用药相同,对照组应用阿托伐他汀钙20mg,拜阿司匹林肠溶片100mg,每晚1次口服;治疗组加用氯吡格雷75mg,1次/d口服,连用14d。观察治疗前后TIA发作的频率变化、脑梗死的发生率及凝血功能、血小板数量、皮肤、消化道情况、血脂、空腹血糖的变化。结果治疗组总有效率95%,对照组为62.5%,2组比较差异有统计学意义,且均未出现严重出血病例。结论阿托伐他汀钙联合氯吡格雷治疗TIA有效且安全。     

氯吡格雷与阿司匹林治疗脑梗死的疗效观察

目的 观察氯吡格雷与阿司匹林治疗脑梗死的疗效.方法 将符合入选标准的142例患者随机分为氯吡格雷组和阿司匹林组,其中氯吡格雷组68例,阿司匹林组74例.分别于治疗前及治疗后第15、30、60和90天对患者进行欧洲脑卒中评分(ESS) 和疗效评定.结果 氯吡格雷组缺血性卒中或TIA发生率(6.25%)低于阿司匹林组(22.9%),2组间比较差异有统计学意义(P< 0.05),氯吡格雷组ESS评分高于治疗前,且高于阿司匹林组,2组间比较差异有统计学意义( P < 0.05) .结论 氯吡格雷治疗脑梗死能有效改善脑梗死患者神经功能缺损和减少再次发生缺血性卒中或短暂性脑缺血发作,是一种较好的治疗脑梗死的方法.     

水蛭素合用阿司匹林与单用阿司匹林或氯吡格雷治疗短暂性脑缺血发作的随机对照研究

目的：探讨水蛭素合用阿司匹林治疗短暂性脑缺血发作（TIA）的疗效和安全性。方法：89例TIA患者随机分为3组：（1）氯吡格雷组（n=29），口服氯吡格雷75mg／d：（2）阿司匹林组（n=30），口服阿司匹林100mg／d；（3）水蛭素合用阿司匹林组（n=30），口服水蛭素0．32g，3次／d，阿司匹林100mg／d。观察治疗后90d内TIA复发或进展为脑梗死的病例数，观察出血等不良事件发生率。结果：治疗后90d内总的脑梗死发生率为4．5％，3组之间无显著差异。水蛭素合用阿司匹林组和氯吡格雷组90d内的TIA复发风险分别较单用阿司匹林降低69％（P=0．0078）和65％（P=0．0170）。总的出血发生率为2．25％，均发生在水蛭素合用阿司匹林组。结论：水蛭素合用阿司匹林可降低90d内TIA复发率的效果优于单用阿司匹林，与单用氯吡格雷相似，但出血风险增高。     

氯吡格雷联合拜阿司匹林治疗老年急性脑梗死疗效观察

目的 探讨氯吡格雷联合拜阿司匹林治疗老年急性脑梗死的疗效和安全性.方法 120例急性脑梗死随机分为三组.治疗组40例,氯吡格雷组40例,拜阿司匹林组40例.在常规治疗基础上,治疗组加用氯吡格雷和拜阿司匹林,氯吡格雷组加用氯吡格雷,拜阿司匹林组加用拜阿司匹林治疗.治疗14d后,观察三组用药前后疗效及安全性.结果 治疗组能明显改善脑梗死局灶神经功能缺损症状(P＜0.05),疗效优于氯吡格雷组和拜阿司匹林组;三组对出凝血指标无明显影响(P＞0.05).结论 氯吡格雷联合拜阿司匹林治疗急性脑梗死安全有效,并能明显改善急性脑梗死患者的局灶神经功能缺损症状,效果优于单独应用氯吡格雷或拜阿司匹林.     

阿司匹林联合氯吡格雷治疗短暂性脑缺血发作的疗效

目的观察阿司匹林联合氯吡格雷治疗短暂性脑缺血发作的疗效。方法选取我院2011-12—2014-12收治的120例短暂性脑缺血患者,分为观察组和对照组各60例,对照组口服阿司匹林常规治疗,观察组采用阿司匹林联合氯吡格雷治疗,观察2组治疗总有效率、外周血血小板水平、药物不良反应等指标。结果经过3个月连续治疗后,观察组治疗总有效率96.7%,对照组为81.7%,差异有统计学意义(P0.05);2组治疗前后血小板水平变化较小,差异无统计学意义(P0.05);2组治疗期间均未发生严重不良反应。结论阿司匹林联合氯吡格雷的治疗方案治疗短暂性脑缺血发作疗效确切,总有效率明显优于单用阿司匹林的治疗效果,不良反应小,值得临床推广应用。     

阿司匹林与氯吡格雷双联对TIA患者凝血功能的影响

目的探讨阿司匹林与氯吡格雷双联对短暂性脑缺血发作(TIA)患者血小板聚集率和纤维蛋白原的影响。方法100例短暂性脑缺血发作患者随机分为2组,在常规控制血压、血糖、血脂等基础上,治疗组给予阿司匹林联合氯吡格雷治疗,对照组给予阿司匹林,其中阿司匹林100mg/d,氯吡格雷75mg/d。观察2组血小板聚集率与纤维蛋白原相关指标及临床疗效。结果治疗7~14d后,与对照组比较,治疗组血小板聚集率显著改善(P0.05),纤维蛋白原水平下降更显著(P0.05);治疗组临床疗效显著优于对照组(P0.05)。2组均未出现严重出血并发症。结论阿司匹林与氯吡格雷双联治疗短暂性脑缺血发作可改善患者血小板聚集率,降低纤维蛋白原水平,临床疗效显著。     

氯吡格雷联合阿司匹林治疗对轻型卒中与短暂性脑缺血发作患者功能预后的影响：CHANCE与POINT试验联合分析

目的 评价氯吡格雷联合阿司匹林双抗治疗对轻型缺血性卒中与TIA患者功能预后的影响。 方法 提取CHANCE和POINT试验所有的个体数据。这两项试验中,所有纳入患者在症状发作12 h （POINT）或24 h（CHANCE）以内随机接受氯吡格雷联用阿司匹林或单用阿司匹林治疗。结局指标为3个 月时功能预后不良（mRS≥2）,三等级定义卒中复发[致残性或致死性卒中复发（mRS≥2）、非致残性 卒中复发（mRS 0或1）、无卒中复发]。 结果 共10 013例患者纳入分析,其中来自CHANCE试验5132例（51.3%）,来自POINT试验4881例 （48.7%）;氯吡格雷联用阿司匹林组4995例（49.9%）,单用阿司匹林组5018例（50.1%）。氯吡格雷联 用阿司匹林组3个月时功能预后不良的患者比例低于单用阿司匹林组（11.6% vs 12.6%,校正OR 0.82, 95%CI 0.72～0.94,P =0.005）。氯吡格雷联用阿司匹林组致残性或致死性卒中复发（4.6% vs 6.1%, 校正OR 0.73,95%CI 0.61～0.87,P <0.001）、非致残性卒中复发（1.9% vs 3.0%,校正OR 0.62,95%CI 0.47～0.80,P <0.001）和卒中复发的整体致残性（校正cOR 0.70,95%CI 0.60～0.81,P <0.001）低于单 用阿司匹林组。 结论 与单用阿司匹林治疗相比,氯吡格雷联用阿司匹林治疗可进一步改善轻型缺血性卒中和TIA 患者3个月时功能预后,减少致残性卒中复发。     

Antiplatelet agents and randomized trials

Patients who have transient ischemic attack (TIA) or ischemic stroke are at a high risk of having a first or recurrent stroke. The annual risk is between 5% and 15%; the risk is highest in the first 48 hours following a TIA and highest in the first 7 days following an ischemic stroke. Secondary prevention includes antithrombotic therapy, treatment of risk factors, and interventional treatment of carotid stenosis. Antithrombotic options can include antiplatelet drugs such as aspirin, aspirin plus extended-release dipyridamole (ER-DP), clopidogrel, or clopidogrel plus aspirin. Oral anticoagulation is used in patients with a cardiac source of embolism such as atrial fibrillation. Aspirin monotherapy offers a modest risk reduction for recurrent stroke and for the combined endpoint of nonfatal stroke, myocardial infarction (MI), and vascular death. The combination of ER-DP and aspirin was shown to be superior to aspirin monotherapy in several trials. Clopidogrel is superior to aspirin in high-risk patients suffering from stroke, MI, or peripheral arterial disease. The combination of clopidogrel plus aspirin is not superior to aspirin or clopidogrel monotherapy and carries a significantly higher bleeding risk. The combination might offer benefit in short-term secondary prevention after TIA or stroke. Another ongoing trial is currently investigating the possible benefit and side effects of aspirin plus ER-DP versus clopidogrel in secondary stroke prevention.     

阿司匹林联合氯吡格雷治疗急性进展性脑梗死的临床观察

目的 观察经阿司匹林治疗后病情仍加重的急性进展性脑梗死(APCI)患者,联合使用氯吡格雷治疗的临床疗效及安全性.方法 76例APCI患者分为治疗组和对照组.治疗组用阿司匹林联合氯吡格雷治疗,对照组单用阿司匹林治疗.在治疗前后对2组患者进行斯堪的那维亚(SSS)评分.结果 治疗组的病情进展持续时间较对照组短;治疗组的SSS评分较对照组高.结论 阿司匹林联合氯吡格雷可延缓APCI的进展.     

Adding aspirin to clopidogrel after TIA and ischemic stroke: benefits do not match risks

Antiplatelet therapy is effective for reducing the risk of recurrent stroke and other serious vascular events in patients with recent TIA and ischemic stroke. Effective antiplatelet agents include aspirin, ticlopidine, clopidogrel, dipyridamole, and the combination of aspirin and dipyridamole. The combination of aspirin and clopidogrel is more effective than aspirin in patients with acute coronary syndrome but is more hazardous than clopidogrel alone in patients with recent TIA and ischemic stroke. Further trials are needed to determine whether the combination of aspirin and clopidogrel may have a role immediately after TIA and ischemic stroke in patients with symptomatic large artery atherothromboembolism and continued for approximately 3 months before switching to less hazardous antiplatelet regimens.     

Aspirin platelet reactivity on platelet function and clinical outcome in minor stroke or transient ischemic attack

ObjectiveWhether aspirin platelet reactivity affects platelet function and clinical outcomes with different antiplatelet therapies in patients with mild stroke or transient ischemic attack (TIA) remains unclear. We conducted a subgroup analysis of the PRINCE trial.Materials and methodsPatients with mild stroke or TIA were randomized into aspirin+ticagrelor, or aspirin+clopidogrel groups; aspirin reaction units (ARU) were measured at the baseline and after 7 ± 2 days to assess response to treatment. High on-treatment platelet reactivity (HPR) was defined as ≥550 ARU (poor response to aspirin). The platelet functions of ticagrelor and clopidogrel were measured using the VerifyNow P2Y₁₂ assay for P2Y₁₂ reaction units (PRU); HPR to P2Y₁₂ was defined as >208 PRU (poor response to P2Y₁₂). Clinical outcomes included stroke and clinical vascular and bleeding events after 90 days.ResultsAmong 628 enrolled patients, 69 (11%) were poor aspirin responders. After 7 ± 2 days, the proportion of poor P2Y₁₂ responders for ticagrelor versus clopidogrel significantly reduced in poor (2.6% versus 27.4%) and good (14.3% versus 29.4%) aspirin responders. There were significant interactions between treatment groups, and between treatment groups and aspirin platelet reactivity for poor P2Y₁₂ responders (P = 0.01). After 90 ± 7 days, there were no significant interactions between treatment groups and aspirin platelet reactivity for new stroke risk (good aspirin responders: 5.5% versus 8.8%, hazard ratio [HR]: 0.61; 95% confidence interval [CI], 0.32 to 1.16; P = 0.13; poor aspirin responders: 8.6% versus 8.8%, HR: 0.97, 95% CI: 0.20–4.81; P = 0.97; P for interaction = 0.60). Major bleeding was less frequent in poor than good aspirin responders (ticagrelor/aspirin: 0.4%/0%; clopidogrel/aspirin: 1.4%/0%).ConclusionsIn patients with minor stroke or TIA, clopidogrel, and particularly ticagrelor, decreased platelet function in poor versus good aspirin responders. The poor platelet reactivity of aspirin could not sufficiently reduce the risk of recurrent stroke with ticagrelor or clopidogrel; however, HPR (poor aspirin response) may have a protective effect on clinically relevant major bleeding.     

氯吡格雷联合阿司匹林治疗青年期急性非心源性脑梗死临床观察

目的观察氯吡格雷联合阿司匹林治疗青年急性脑梗死的疗效及不良反应。方法选择80例急性非心源性脑梗死的青年患者,随机分为观察组(n=40)和对照组(n=40)。观察组给予阿司匹林和氯吡格雷,对照组给予阿司匹林和安慰剂。根据卒中临床神经功能缺损评定标准(NIHSS)和日常生活能力(ADL)评分标准进行评定,并监测血清hs-CRP水平。结果治疗后21d,观察组NIHSS、ADL评分均明显优于对照组,观察组有效率显著好于对照组,hs-CRP水平明显降低,差异均有统计学意义(P0.05),且不良反应可耐受。结论氯吡格雷联合阿司匹林能明显改善急性非心源性脑梗死青年患者的预后,且较安全,有进一步研究的价值。     

2012-2014年北京缺血性卒中患者阿司匹林和氯吡格雷联合使用率分析

目的 通过大数据分析我国临床缺血性卒中患者阿司匹林联合氯吡格雷（双抗）的使用率情况。
方法 从北京市职工医疗保险系统数据库中提取2012年1月-2014年12月,根据国际疾病分类
（International Classification of Diseases,ICD）-10编码主诊断为I63（缺血性卒中）和G45[短暂性脑缺血发
作（transient ischemic attack,TIA）和相关的综合征]的患者,以2013年6月为界限分为前后各18个月,比
较这两个阶段患者用药记录中阿司匹林联合氯吡格雷用药的使用比例。并按照主诊断为缺血性卒中
和TIA进行亚组分析。
结果 研究期间共纳入用药记录6 296 188例次,患者总计101 587例。2013年7月-2014年12月,每个
月双抗使用876.9例次（标准差129.8）,中位数867（最小值511、最大值1112）,占比14.7%。而2012年1
月-2013年6月每个月的双抗使用649.9例次（标准差129.8）,中位数650.5（最小值352、最大值895）,
占比12.3%。2013年6月以后,主诊断为缺血性卒中和TIA的患者每月双抗使用比例分别为20.2%和
11.1%,而2013年6月之前每月双抗的比例为14.5%和9.1%,2013年6月之后的双抗使用比例大于2013
年6月之前。2013年6月前双抗的使用人数占入选患者的18.3%,而2013年6月之后接受双抗治疗的患
者比例提高至22.2%。
结论 在北京市医疗保险缺血性卒中和TIA患者中,相比2013年6月前,2013年6月后使用阿司匹林联
合氯吡格雷进行双抗的比例较高。     

Combined clopidogrel–aspirin treatment for high risk TIA or minor stroke does not increase cerebral microbleeds

Abstract

Objectives:

To study whether Clopidogrel–Aspirin combined treatment for high risk transient ischaemic attack (TIA) or minor stroke results in increased number of lesions associated with anti-thrombotic cerebral haemorrhage or cerebral micro-bleeds (CMB) than aspirin alone treatment.

Methods:

The patients recruited in CHANCE test in our hospital participated in this study. We made a comparison between treatments Aspirin–Clopidogrel combined group and the Aspirin alone group in the numbers of CMB and subsequent cerebral haemorrhages. In addition, we analysed the association between the increased numbers of CMB and subsequent intracerebral haemorrhages. All 129 patients with high risk TIA with microbleeds or minor stroke within 24?hours after the onset (average age 65.9?±?9.3, 48.7% were male patients) were divided randomly into two groups: (1) 67 patients were given combination therapy with clopidogrel and aspirin (clopidogrel at an initial dose of 300?mg, then 75?mg per day for 90?days, plus aspirin at a dose of 75?mg per day for the first 21?days);(2) the rest patients were given aspirin treatment (75?mg per day for 90?days). All participants received open-label aspirin at a clinician-determined dose of 75–300?mg on the first day.

Results:

The CMB were found in 52.7% of all patients in both groups. There was no siginificant difference between the Aspirin group and the Aspirin–clopidogrel treated group, though the latter showed some slight increase in CMB (Odds ratios (OR)?=?1.16, 95% confidence intervals (CI) =?0.54–2.47, P?=?0.71). But the numbers of CMB were remarkably associated with the number of primary existing CMB (OR?=?6.46, 95%CI 2.57–16.23, P?<?0.001), especially that of primary existing CMB ≥?3.In addition, the increasing numbers of CMB associated with primary CMB lesions, which located in corticosubcortical area (CSC) (OR?=?4.69, 95%CI 1.51–14.53, P?=?0.007).

Conclusions:

For the treatment of high-risk TIA or minor stroke patients, the clopidogrel–aspirin treatment did not increase the number of CMB than Aspirin alone. It appears that the extent of CMB was associated with the extent of existing CMB occurred in previous stroke, which was mostly located in cortical, subcortical zone.