强化抗血小板治疗在缺血性脑卒中复发高危患者二级预防中的临床研究

目的观察强化抗血小板药物氯吡格雷在缺血性脑卒中复发高危患者二级预防中的长期疗效及安全性。方法采用艾森卒中风险评分（ESRS）量表筛选住院的急性非心源性缺血性脑卒中复发高危患者100例,随机分为氯吡格雷组和阿司匹林组,每组50例。两组均给予脑卒中常规治疗,氯吡格雷组予氯吡格雷75mg及阿司匹林100mg口服,1周后仅予氯吡格雷75mg,口服。阿司匹林组予阿司匹林200mg,口服,1周后改为100mg,口服。随访3个月和1年,观察两组缺血性脑卒中复发率及药物不良反应发生率。结果随访3个月时,脑卒中复发率：阿司匹林组为6．3％,氯吡格雷组为2．0％,差异无统计学意义（P〉0．05）;药物不良反应发生率：阿司匹林组为14％,氯吡格雷组为2％,差异有统计学意义（P〈0．05）。随访1年时,脑卒中复发率：阿司匹林组为13％,氯吡格雷组为2％,差异有统计学意义（P〈0．05）;药物不良反应发生率：阿司匹林组为38％,氯吡格雷组为6％,差异有统计学意义（P〈0．01）。结论缺血性脑卒中复发高危患者二级预防中强化抗血小板治疗可降低脑卒中复发风险,长期应用获益较高,安全性好。     

缺血性脑卒中二级预防中阿司匹林与氯吡格雷的不良反应

目的探讨阿司匹林与氯吡格雷在缺血性脑卒中二级预防中的不良反应,为临床研究提供参考。方法选择在我院进行二级预防的缺血性脑卒中82例,随机分为阿司匹林组40例与氯吡格雷组42例。阿司匹林组口服阿司匹林100mg/d,氯吡格雷组口服氯吡格雷1mg/d,长期密切随访,对出现的消化道不良反应、脑卒中复发、TIA事件、颅内出血、泌尿道及皮肤黏膜出血进行统计,评价阿司匹林与氯吡格雷的用药安全性。结果阿司匹林组总消化道不良反应发生率为40.0%,均显著高于氯吡格雷组(P0.05)。阿司匹林组发生消化道出血和消化道溃疡例数均为4例,与氯吡格雷组比较差异无统计学意义(P0.05);阿司匹林组各种临床事件与氯吡格雷组比较差异无统计学意义(P0.05)。结论阿司匹林消化道不良反应率显著高于氯吡格雷,但消化道出血、消化道溃疡、脑卒中复发、TIA事件以及颅脑、泌尿道与皮肤黏膜出血等严重不良事件差异无统计学意义(P0.05)。     

双联抗血小板治疗非心源性缺血性脑卒中的有效性及安全性

目的探讨双联抗血小板治疗非心源性缺血性脑卒中的临床疗效和安全性。方法选取我院就诊的非心源性缺血性脑卒中患者150例,随机分为2组,每组75例。2组均给予相同的基础治疗以及强化他汀类药物治疗,在此基础上,试验组于入院当日口服拜阿司匹林300mg,硫酸氢氯吡格雷300mg,第2天开始每日口服拜阿司匹林100mg,硫酸氢氯吡格雷75mg;对照组于入院当天口服拜阿司匹林300mg,第2天开始改为每日口服拜阿司匹林100mg。治疗4周后,观察比较2组的治疗效果、实验室指标、不良反应发生率、复发率情况。结果试验组总有效率85.33%,对照组为65.33%,差异有统计学意义(P0.05);试验组血小板聚集率、血浆黏度、全血低切黏度明显低于对照组;2组不良反应发生率无明显差异(P0.05);试验组2例复发,复发率为2.67%,对照组10例复发,复发率13.33%,试验组复发率低于对照组(P0.05)。结论双联抗血小板治疗非心源性脑卒中临床疗效满意,复发率较低,且无明显不良反应,安全性良好。     

血栓弹力图评价缺血性脑血管病患者服用不同小剂量阿司匹林疗效

抗血小板药物能显著降低非心源性脑缺血性卒中或TIA患者再次严重血管事件的发生率[1].阿司匹林和氯吡格雷是经循证医学证实可常规应用的抗血小板聚集药,2010年中国缺血性卒中或TIA发作二级防治指南及2011年AHA/ASA关于缺血性卒中或TIA发作患者卒中预防指南指出:对于非心源性缺血性卒中和TIA的抗栓治疗,氯吡格雷75mg和阿司匹林50mg～325mg均可作为首选药物[2,3].     

氯吡格雷/阿司匹林双抗预防非心源性缺血性脑卒中的效果观察

目的观察氯吡格雷联合阿司匹林双抗防治非心源性缺血性脑卒中的临床效果。方法选取2011-05—2014-05收治的非心源性缺血性脑卒中患者114例,随机分为观察组与对照组,2组均常规卒中治疗,在此基础上对照组单纯应用阿司匹林,观察组使用氯吡格雷联合阿司匹林治疗,观察2组临床效果。结果观察组3个月、1a内复发率均明显低于对照组,总不良反应率低于对照组,差异均有统计学意义(P0.05)。结论对非心源性缺血性脑卒中患者使用氯吡格雷联合阿司匹林进行双抗防治,能够有效降低其卒中复发率,减少不良反应,在临床防治中有较理想的效果。     

氯吡格雷预防非瓣膜病性心房颤动血栓栓塞的疗效观察

目的 观察氯吡格雷对非瓣膜病性心房颤动患者血栓栓塞并发症的预防效果和安全性.方法 选取非瓣膜病性心房颤动患者96例随机分为2组,对照组常规以肠溶阿司匹林抗血小板治疗,150mg,1次/d;治疗组于肠溶阿司匹林100mg,在1次/d基础上加用氯吡格雷首剂负荷量300mg,以后50mg,1次/d,2组随访时间均为1.5年,观察2组1.5年内血栓栓塞并发症及出血等不良反应发生率,进行比较.结果 治疗组用药后1.5年内血栓栓塞发生率为10%,对照组血栓栓塞发生率为36.96%,2组比较差异有统计学意义(P＜0.01),出血等不良反应无明显差异.结论 氯吡格雷能降低非瓣膜病房颤血栓栓塞发生率,安全有效,值得临床推广应用.     

吸烟状态对氯吡格雷疗效的影响

目的通过血栓弹力图检测,观察吸烟状态是否会对缺血性卒中患者的氯吡格雷疗效产生影响。方法回顾性连续纳入2013年1月-2014年10月首次发病的急性非心源性栓塞所致的缺血性脑血管病并接受氯吡格雷治疗的患者202例,分为吸烟组和不吸烟组。连续服用氯吡格雷每日75 mg,5 d后,抽取外周静脉血,用血栓弹力图仪测定氯吡格雷对血小板的抑制率。结果与非吸烟组相比,吸烟组患者氯吡格雷诱导的二磷酸腺苷抑制率更高(55.29%±25.92%vs 53.25%±27.02%,P=0.589),出现氯吡格雷反应低下(二磷酸腺苷抑制率30%)的患者比例更低(15.8%vs 19.5%,P=0.498),但差异无统计学意义。结论在非心源性栓塞的缺血性卒中患者中,吸烟有提高氯吡格雷反应性,增强其抗血小板聚集作用的趋势。但吸烟者中氯吡格雷治疗后血小板反应的变异性仍有待进一步研究证实。     

不同抗血小板聚集治疗方案对高原缺血性卒中治疗对比研究

目的 研究应用不同的抗血小板聚集治疗方案对高原缺血性卒中临床治疗效果的影响。 方法 收集青海省人民医院神经内科自2014年3月-2015年3月收治的发病24 h内的急性缺血性卒中 患者90例,随机分为阿司匹林单药治疗组和氯吡格雷联合阿司匹林治疗组,两组患者均进行相应的 内科综合治疗,其中阿司匹林单药治疗组在前者基础上服用阿司匹林（100 mg/d）,氯吡格雷和阿司 匹林联合治疗组则在综合治疗的基础上采用氯吡格雷-阿司匹林联合治疗方案（阿司匹林100 mg/d, 氯吡格雷75 mg/d）,对比两组患者治疗后14 d和28 d美国国立卫生研究院卒中量表（National Institutes of Health Stroke Scale,NIHSS）评分变化情况、进展性卒中发生率以及出血转化率和死亡率情况。 结果 两组治疗后比同组治疗前NIHSS均有显著降低,联合治疗组治疗后14 d及28 d NIHSS评分为5（3, 7）和4（3,6）,显著低于单药治疗组同期NI HSS评分[7（5,9）和6（4,8）]（P分别为0.03和0.02）。联合 治疗组中进展性卒中发生率为11.1%（5例）,显著低于单药治疗组的35.5%（16例）（P =0.04）。两组 28 d内缺血性卒中后出血转化率及死亡率方面无显著差异。 结论 氯吡格雷联合阿司匹林治疗方案表现出对急性高原性缺血性卒中良好的治疗效果,且不增 加出血转化的风险。     

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。     

ABCD3-Ⅰ评分在短暂性脑缺血发作预防与治疗中的应用

目的探讨ABCD3-Ⅰ评分系统评价阿司匹林单药及其与氯吡格雷联合治疗短暂性脑缺血发作的有效性和安全性。方法 122例短暂性脑缺血发作患者分别接受阿司匹林单药(单抗组)或阿司匹林与氯吡格雷联合(双抗组)治疗,并根据ABCD3-Ⅰ评分系统进一步分为低危组、中危组和高危组,评价各亚组患者缺血性卒中和药物不良反应发生率。结果治疗3周时,低危组无一例发生缺血性卒中,其他各组分别为:中危单抗组9/20例、中危双抗组2/19例,高危单抗组10/19例、高危双抗组3/20例,组间差异有统计学意义(P=0.031,0.019)。单抗组和双抗组患者药物不良反应均以恶心、反酸等消化道症状为主(χ2=0.000,P=1.000),无明显出血倾向、肝肾功能未见异常。结论 ABCD3-Ⅰ评分系统可以作为评价抗血小板药物安全性的指标。阿司匹林联合氯吡格雷可能较阿司匹林单药预防缺血性卒中更具优势。     

基于高分辨率磁共振成像的氯吡格雷和阿司匹林治疗症状性颅内动脉狭窄患者1年的疗效观察

目的 通过高分辨率磁共振成像观察硫酸氢氯吡格雷片和阿司匹林肠溶片治疗症状性颅内动脉狭窄（intracranial artery stenosis,IAS）的有效性及安全性,旨在为症状性IAS患者的药物治疗选择提供可靠依据。      

Results of the management of atherothrombosis with clopidogrel in high-risk patients trial: implications for the neurologist

The secondary prevention of ischemic stroke is aided by the use of antiplatelet therapy, and the predominant current choices are aspirin, aspirin plus extended-release dipyridamole, and clopidogrel. The potential utility of combining platelet antiaggregants with different mechanisms of action proved successful with aspirin plus extended-release dipyridamole, and this approach has been explored with the combination of clopidogrel and aspirin. In the Management of Atherothrombosis With Clopidogrel in High-Risk Patients trial, this combination was compared with clopidogrel alone for secondary prevention in patients with transient ischemic attack and stroke in a high-risk population with a high prevalence of other vascular risk factors. A nonsignificant trend for a reduction of the combined endpoint of ischemic stroke, myocardial infarction, vascular death, and rehospitalization was observed in the combination therapy group (P = .24). The frequency of serious, life-threatening bleeding adverse effects was almost doubled in the combination arm. Neurologists need to be aware of these results and avoid the use of clopidogrel plus aspirin in patients with stroke or transient ischemic attack until evidence that the combination is safe in this population is provided. Neurologists faced with patients who have had a stroke or transient ischemic attack and are receiving this combination of antiplatelet agents after coronary stenting should inform their cardiology colleagues of the reported bleeding risk, and they should encourage the use of the combination for as short a time period as possible after such coronary intervention.     

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.     

A Randomized trial comparing ticlopidine with aspirin fof the prevention of ischemic cerebral stroke

OBJECTIVE To assess the effect and cafety of t iclopidine in the prevention of ischemic cerebral stroke and to compare theeffect of low-dose aspirin with t iclopidine. BACKGROUND The effect and safety of ticlopidine irn the prevention of ischemic cerebral stroke in China has not been reported. METHODS 329 patients with TIA or mild ischemic cevebral stroke wasrandonmly assigned to ticlopidine group(165 case) or aspirin group (164 case) in this study.These patrents were randomly allocated to receive either 250mg trclopidine or 50mg aspirin daily and didnd take any other platelet antiaggregating drugs. Time of eacn follow up visit was one to two months. Follow up lasted for 6 to 18 months. RESULTS The event rate for stroke or death from any cause was 8.3% in ticlopidine group arid 14.9% in aspirin group. This repesented a risk reduction of 44.3%(95% cofidence interval, 0.29-0.94) for ticiopidine group as compared with aspirin group. The event raite for ischemic cerebral stroke or myocarction of ticlopidine group(7.0%)was lower than that cf aspirin group(14.8%)(P＜0.05).A riskreduction of 52.7%(95% confidence interval,0.24-0.92) for ticlopidine group compared with aspirin group. The rate of adverse effects of ticlopidine group and aspirin group were 6.9% and 11.0% during the trial ,but this was not statistically significant(P＜0.05).DISCUSSION and CONCLUSION Therapeutic efficacy for the prevention oi ischemic stroke of ticlopidine was better than that of aspirin, the rate of side effects in ticlopidine group and aspirin group are not statistically significant. So ticiopidine could serve as a first-line drug for the prevention of ischemic stroke.     

阿加曲班治疗急性缺血性卒中的临床应用

阿加曲班是一种直接凝血酶抑制剂,具有起效较快、作用时间短、出血倾向小、无免疫源性等优点,能够有效阻止血栓进展,防止继发微血栓形成。国内外多项研究证实,阿加曲班能有效改善急性缺血性卒中患者的神经系统症状和日常活动能力,且对急性动脉粥样硬化性卒中和心源性卒中均有治疗作用,此外,阿加曲班与阿司匹林、奥扎格雷等抗血小板药物以及肝素相比疗效更显著,具有较高的安全性,同时由于作用机制不同,阿加曲班与阿司匹林、氯吡格雷等抗血小板药物、重组组织型纤溶酶原激活物(recombinant tissue plasminogen activator,rt-PA)联合治疗可能发挥协同作用。本文就阿加曲班在急性缺血性卒中的临床应用做一系统性综述。     

The PRoFESS trial: future impact on secondary stroke prevention

Patients with transient ischemic attack and ischemic stroke have a high risk of recurrent stroke and death. While aspirin is accepted as standard therapy in these patients, recent trials demonstrate that a combination of aspirin and extended-release dipyridamole or clopidogrel is superior to aspirin monotherapy. Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers may also reduce recurrent stroke. The ongoing Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial is designed to evaluate whether extended-release dipyridamole plus aspirin compared with clopidogrel, and whether telmisartan in addition to usual care, in individuals after a stroke, will reduce the risk of further strokes. PRoFESS is a multicenter, randomized, double-blind trial involving 695 sites from 35 countries or regions. The primary outcome for the trial is recurrent stroke, using a time-to-event analysis. Safety is evaluated by assessing the risk of major hemorrhagic and other serious adverse events. With over 20,000 patients randomized, and utilizing a 2 x 2 factorial design, PRoFESS is the largest stroke trial to investigate the prevention of recurrent stroke.     

Antiplatelets in stroke prevention: the MATCH trial. Some answers, many questions and countless perspectives

Antiplatelet drugs have an established efficacy in the secondary prevention of ischemic stroke. The recent results of the CAPRIE, CURE, and CREDO studies formed the rationale for the MATCH, designed to test whether the association of clopidogrel and aspirin was better than clopidogrel alone for the prevention of vascular events among high-risk ischemic cerebrovascular patients. Although the benefits were outweighed for a higher bleeding risk in the combination group, this study will provide important insight for upcoming trials in other to determine what populations might mostly benefit from these drugs for the secondary prevention of stroke in the future.     

Antiplatelet therapy for secondary prevention of noncardioembolic ischemic stroke: a critical review

For patients with ischemic stroke or transient ischemic attack caused by atherothromboembolism, immediate and long-term aspirin reduces the relative risk of recurrent stroke, MI, and death attributable to vascular causes. Oral anticoagulation is not more effective than aspirin. Long-term clopidogrel reduces the relative risk of stroke, MI, or vascular death by about 9% (0.3% to 16.5%) compared with aspirin. Any long-term benefits of clopidogrel combined with aspirin, compared with aspirin or clopidogrel alone, appear to be offset by increased major bleeding. The combination of aspirin and extended-release dipyridamole reduces the relative odds of stroke, MI, or vascular death by about 18% (odds ratio 0.82, 0.74 to 0.91) compared with aspirin alone without causing more bleeding. Cilostazole reduces the risk of stroke, MI, or vascular death by 39% compared to placebo. A large clinical trial comparing clopidogrel with the combination of aspirin and dipyridamole, in >20 000 patients with recent (<120 days) atherothrombotic ischemic stroke, is expected to report in 2008. Emerging antiplatelet therapies presently being evaluated for secondary prevention of atherothromboembolism include other P(2)Y(12) ADP receptor antagonists (prasugrel, cangrelor, AZD 6140), thromboxane receptor antagonists (eg, S18886 - terutroban), and thrombin receptor (PAR-1) antagonists (eg, SCH530348).     

Antithrombotic and anticoagulation therapy after stroke and transient ischemic attacks

Patients with a transient ischemic attack (TIA) or ischemic stroke are at high risk for a recurrent stroke. Platelet inhibitors can reduce this risk in patients with non-cardioembolic stroke or TIA. Aspirin is used for secondary prevention in patients with a low risk of recurrent stroke while the combination of aspirin and dipyridamole or clopidogrel is recommended in patients with a higher risk. Patients with atrial fibrillation have a five-fold increased risk of stroke. In comparison to placebo oral anticoagulation reduces the risk of stroke by 60-70% in primary and secondary stroke prevention. Aspirin can still reduce the relative stroke risk by 22% in patients with atrial fibrillation who have contraindications against anticoagulation. Given the limitations of oral anticoagulation with vitamin K antagonists a new generation of anticoagulants is currently being investigated which include factor Xa inhibitors and direct thrombin antagonists. Dabigatran has been shown to be as efficacious as warfarin given at a lower dose and significantly more efficacious when administered at a higher dosage. Both cerebral and intracranial hemorrhages were reduced by 60-80% in patients treated with dabigatran when compared to warfarin.