氯吡格雷对缺血性脑血管病的二级预防

目的观察氯吡格雷与阿司匹林对缺血性脑血管病复发的影响。方法将2002年1月-2005年1月收治的急性脑梗死患者269例，分为氯吡格雷组（137例），阿司匹林（132例），出院后的1、3、6、12个月各随访1次。主要指标：（1）缺血性脑血管病复发或短暂性脑缺血发作（TIA）；（2）经CT诊断的脑出血；（3）消化道或皮肤出血。结果氯吡格雷组缺血性脑血管病复发和TIA的发生率（5．84％）低于阿司匹林组（26．52％），差异有显著性（P〈0．05）；氯吡格雷组出血发生率（6．57％）低于阿司匹林组（6．82％），差异无显著性（P〉0．05）。结论氯吡格雷对预防缺血性脑血管病复发的效果优于阿司匹林，并未增加出血性并发症。     

氯吡格雷联合丹红注射液治疗不稳定型心绞痛疗效观察

目的观察氯毗格雷联合丹红注射液治疗不稳定型心绞痛（UAP）的临床疗效。方法将80例UAP患者随机分为治疗组与对照组各40例。两组均给予常规治疗;对照组加用阿司匹林与低分子肝素;治疗组氯吡格雷首次顿服300mg,次日起75mg/d,同时丹红注射液30ml加入生理盐水250ml中静脉滴注,1次／d;两组疗程均为2周。观察两组心电图、心绞痛改善情况以及血清高敏C反应蛋白（hs-CRP）水平变化。结果与对照组比较,治疗组临床症状及心电图表现均明显改善（P均〈0．05）,血清hs-CRP水平显著降低（P〈0．05）。结论氯吡格雷联合丹红注射液控制心绞痛发作效果良好。     

负荷剂量氯吡格雷联合阿司匹林治疗后循环短暂性脑缺血发作疗效观察

目的　观察负荷剂量氯吡格雷联合阿司匹林治疗后循环短暂性脑缺血发作（TIA）的疗效和安全性。方法　选择本院2011年5月至2013年10月住院的后循环TIA患者84例，随机分为两组，42例给予口服阿司匹林为对照组，42例给予负荷剂量氯吡格雷及阿司匹林为治疗组，治疗4周后评价治疗效果，并比较两组血小板计数及脑微出血等不良反应情况。结果　治疗4周后，治疗组疗效显著优于对照组（显效率为57.14%比35.71%，P<0.05；总有效率为85.71%比54.76%，P<0.05）；两组内治疗前后及治疗后组间血小板计数、脑微出血比较差异无统计学意义（P>0.05）。结论　负荷剂量氯吡格雷联合阿司匹林治疗后循环TIA安全有效，无明显不良反应，值得临床推广。     

氯吡格雷联合阿司匹林对TIA患者凝血及纤溶指标的影响

目的 观察氯吡格雷联合阿司匹林对短暂性脑缺血发作（TIA）患者凝血及纤溶系统的影响。方法 将66例TIA患者随机分为观察组和对照组各33例,两组均口服阿司匹林100mg／d,在此基础上观察组口服氯吡格雷50mg／d。分别于治疗前及治疗后7d抽取空腹静脉血检测PT、AIWT等凝血及纤溶系统指标;观察药物不良反应发生情况。结果两组治疗后凝血及纤溶系统指标均有所改善,尤以观察组为著;两组不良反应发生率无显著差异。结论氯吡格雷联合阿司匹林可有效调节TIA患者凝血及纤溶系统平衡,且安全性高。     

大剂量氯吡格雷治疗进展性脑梗死34例临床观察

目的探讨大剂量氯吡格雷（商品名：波立维）治疗进展性脑梗死的临床效果。方法选择确诊的进展性脑梗死患者68例,随机分为对照组和观察组,每组34例。两组均给予脑梗死常规治疗,对照组加用氯吡格雷75mg和阿司匹林100mg,观察组加用氯吡格雷150mg和阿司匹林100mg。在治疗前后对两组患者进行疗效评价和安全性评估。结果治疗结束后,两组患者神经功能评分较治疗前明显改善,差异有统计学意义（P〈0．05）,观察组改善比对照组明显,两组比较差异有统计学意义（P〈0．05）;观察组患者治疗显著率高于对照组（P〈0．05）,但两组治疗总有效率差异无统计学意义（P〉0．05）;两组患者出血事件发生率差异没有统计学意义（P〉0．05）。结论氯吡格雷150mg／d治疗量,可有效控制进展性脑梗死。     

氯吡格雷联合阿司匹林治疗急性脑梗死38例疗效观察

目的探讨氯吡格雷联合阿司匹林治疗急性脑梗死的疗效及安全性。方法将76例急性脑梗死患者随机分为观察组和对照组,每组38例,两组患者均予降低颅内压、降血脂、钙离子拮抗剂、活血化瘀中药、营养支持等治疗。在此基础上,对照组患者予注射用奥扎格雷钠80mg静脉滴注,2次／d;观察组患者予氯吡格雷片口服,75mg／次·d,阿司匹林片100mg／次·d,口服。两组均连用14d为l疗程。疗程结束后比较两组患者的临床疗效及神经功能缺损评分情况。结果观察组患者治疗总有效率达（92．1％）,明显优于对照组（68．4％）,差异有统计学意义（P〈0．05）。治疗后两组患者神经功能缺损评分均较治疗前明显下降（P均〈0．01）,且观察组患者下降幅度更明显（P〈0．01）。两组患者治疗期间均未发生明显不良反应。结论氯吡格雷联合阿司匹林治疗急性脑梗死有较好的疗效,能明显改善患者的神经功能,值得推广应用,、     

尿激酶联合氯吡格雷阿司匹林治疗急性ST段抬高型心肌梗塞疗效

目的：观察尿激酶溶栓联合氯吡格雷、阿司匹林治疗急性ST段抬高型心肌梗塞（STEMI）的临床疗效及安全性。方法：87例STEMI符合溶栓治疗患者,被随机分为两组,常规治疗组（40例）和氯吡格雷组（47例）,两组溶栓前均给予阿司匹林0．3g口服,氯吡格雷组于入院后即刻口服氯吡格雷300mg,次日改为75mg,1次／d,口服。观察两组治疗的血管再通率,30d内的主要心血管不良事件（死亡、AMI、恶性心律失常、肺水肿等）的发生率。结果：较之对照组,氯吡格雷组梗塞相关血管再通率明显提高（60．3％：74．5％,P〈0．05）,梗塞后心绞痛发生率、30d死亡及再发心肌梗塞率、严重心律失常发生率、肺水肿发生率均显著下降（P〈0．05）。结论：尿激酶溶栓联合氯吡格雷、阿司匹林治疗急性ST段抬高型心肌梗塞是安全有效的。     

抗血小板药物对脑梗死患者血小板-白细胞聚集体的影响

目的观察急性脑梗死患者血小板一白细胞聚集体（PLA）的变化以及阿司匹林和氯吡格雷对其的影响。方法对急性脑梗死和对照组患者血小板聚集率（PAR）、可溶性P选择素（sP—sel）、C-反应蛋白（CRP）和PLA进行检测。同时将急性脑梗死患者随机分为阿司匹林组和氯吡格雷组,观察两组患者治疗前后斯堪的纳维亚神经卒中量表（SNSS）评分、PAR、sP—sel、CRP和PLA的变化。结果急性脑梗死患者血小板单核细胞聚集体（PMA）显著高于对照组（P〈0．001）;PMA水平与PAR、sP-sel、CRP、血糖、胆固醇和纤维蛋白原正相关（P〈0．05）;与SNSS评分负相关（P〈0．05）。脑梗死患者治疗后PMA、PAR明显下降（P≤0．001）,且治疗后氯吡格雷组PMA和PAR（ADP）降低较阿司匹林组更明显（P〈0．05）,但PAR（AA）两组间差异无统计学意义;sP-sel在氯吡格雷组治疗后显著下降（P〈0．001）。结论急性脑梗死患者反映血小板活化的敏感指标PMA明显增高,阿司匹林和氯吡格雷可以降低PMA水平,其中氯吡格雷作用较阿司匹林更为明显。     

水蛭素合用阿司匹林与氯吡格雷治疗TIA的疗效和卫生经济学比较

目的比较水蛭素合用阿司匹林与氯吡格雷治疗短暂性脑缺血发作（TIA）的疗效和卫生经济学差异。方法59例TIA随机分成两组,实验组口服水蛭素0．32g／次,3次／d,阿司匹林100mg／d;对照组口服氯吡格雷75mg／d,观察治疗后90d内的治疗效果,比较两组不同时期内缺血性脑血管事件的病例数、出血等不良事件的发生率和治疗费用。结果两组在降低90d内缺血性脑血管事件方面无显著性差异。水蛭素合用阿司匹林组的治疗费用为单用氯吡格雷的42％。两组出血发生率无显著性差异。结论水蛭素合用阿司匹林降低TIA患者90d内缺血性脑血管事件风险的疗效与单用氯吡格雷相似,而治疗费用显著低于氯吡格雷,但可能会增加出血的风险。     

抗血小板药预防缺血性卒中患者缺血事件再发

目的：比较氯吡格雷、阿司匹林和阿司匹林加双嘧达莫对缺血性卒中患者再次发生缺血事件的影响。方法：2003年1月-2005年1月收治的急性脑梗死患者314例，分为氯吡格雷组（82例，75mg/d）、阿司匹林组（106例，肠溶阿司匹林75—100mg/d）和阿司匹林加双嘧达莫组（126例，阿司匹林肠溶75～100mg/d和双嘧达莫150mg/d）。至少在出院后1、3、6、12个月各随访1次。主要终点指标：（1）再次缺血性卒中或短暂性脑缺血发作（TLA）；（2）经CT证实的脑出血；（3）外周血管血栓栓塞；（4）出现胃肠道、眼底或皮肤出血。结果：氯吡格雷组缺血性卒中和TIA的发生率（6．1％）低于阿司匹林组（26．7％，P〈0．05）或阿司匹林加双嘧达莫组（20．6％，P〈0．05），阿司匹林组与阿司匹林加双嘧达莫组组无显著差异（P〉0．05）。氯吡格雷组出血发生率为7．32％，低于阿司匹林组（7．62％）或阿司匹林加双嘧达莫组（7．94％），但无统计学差异（P〉0．05）。结论：氯吡格雷预防缺血事件再发的效果优于阿司匹林或阿司匹林加双嘧达莫，且并未增加出血性并发症。     

氯吡格雷在短暂性脑缺血发作后脑卒中二级预防中的应用

目的探讨氯吡格雷在短暂性脑缺血发作(transient ischemic attack,TIA)后预防缺血性脑卒中发作的疗效。方法选择TIA患者279例,随机分为2组:氯吡格雷组158例(氯吡格雷75 mg,1次/d),长效阿司匹林组121例(拜阿司匹林100 mg,1次/d)。患者随访1.5～3.0(2.3±0.3)年,评估2组的安全性。结果氯吡格雷组患者缺血性脑卒中复发率明显低于长效阿司匹林组,差异有统计学意义(5.06% vs 12.40%,P0.05)。全部患者在TIA后缺血性脑卒中复发的危险比为0.4031,氯吡格雷组为0.1284,长效阿司匹林组为0.8129,差异有统计学意义(P0.05)。氯吡格雷组患者发生次要事件概率和胃肠道出血事件明显低于长效阿司匹林组,差异有统计学意义(1.90% vs 8.26%,1.27% vs 6.61%,P0.05)。结论氯吡格雷对TIA患者的缺血性脑卒中的预防,优于长效阿司匹林。     

大剂量氯吡格雷联合阿司匹林、尿激酶溶栓治疗急性ST段抬高型心肌梗死的疗效观察

目的:探讨大剂量氯吡格雷联合阿司匹林、尿激酶溶栓治疗急性ST段抬高型心肌梗死(STEMI)的临床疗效。方法:将70例STEMI患者随机等量分为两组,在尿激酶溶栓的基础上,试药组进行大剂量氯吡格雷联合阿司匹林治疗,对照组只进行常规阿司匹林治疗,治疗1周后观察比较两组的疗效和安全性。结果:两组复合终点事件的差异显著,试药组的近期疗效显著优于对照组(P0.05),两组的出血发生率无显著差异。结论:STEMI患者在应用阿司匹林,尿激酶治疗基础上加用大剂量氯吡格雷,可显著降低住院期间的病死率和心血管事件的发生。     

低分子肝素治疗不稳定心绞痛疗效观察

目的:探讨低分子肝素(LMWH)治疗不稳定心绞痛(UAP)的临床疗效。方法:选择UAP 716例患者为观察对象。患者被随机分为4组:A组:阿司匹林组,B组:阿司匹林+氯吡格雷组,C组:阿司匹林+LMWH组,D组:阿司匹林+氯吡格雷+LMWH组。观察指标:治疗前、后的心绞痛,血脂、凝血系列状况,心电图(ECG)。结果:阿司匹林+氯吡格雷+LMWH疗效最佳,可显著减少心肌缺血时间(P<0.01),改善血脂、Holter ECG异常(P<0.01)。LMWH能提升高密度脂蛋白水平,降低低密度脂蛋白和胆固醇水平。阿司匹林、氯吡格雷、LMWH对APTT均无影响。阿司匹林、氯吡格雷可使PTINR显著延长,LMWH对PTINR无显著影响。结论:阿司匹林+氯吡格雷+LMWH治疗UAP临床疗效最佳,LMWH对凝血系列无显著影响。     

Secondary stroke prevention with antiplatelet therapy with emphasis on the cardiac patient: a neurologist's view

The prevention of secondary vascular events is of paramount importance in patients with a history of stroke or transient ischemic attack (TIA). Most cardiologists are aware of the benefits of clopidogrel plus aspirin versus those of other antiplatelet regimens in patients with acute coronary syndrome. Using a representative post-stroke patient as an example, this article reviews data evaluating the effectiveness of antiplatelet regimens in preventing secondary vascular events in stroke and TIA patients. These results differ from those seen in clinical trials of acute coronary syndrome patients. Clinical studies provide little evidence that clopidogrel, with or without aspirin, is more efficacious in this setting than aspirin alone. Moreover, the increased risk of bleeding episodes with clopidogrel and aspirin in combination probably outweighs any small reductions in secondary event risk. In contrast, extended-release dipyridamole (ER-DP) plus aspirin reduces secondary stroke risk to a significantly greater extent (23% relative risk reduction) than aspirin alone. Currently available clinical trial data support the use of ER-DP plus aspirin, but not clopidogrel plus aspirin, to prevent secondary vascular events after stroke or TIA.     

MATCH results: implications for the internist

The long-awaited results of the Management of Atherothrombosis with Clopidogrel in High-Risk Patients with Recent Transient Ischemic Attack (MATCH) study, a large-scale trial undertaken to evaluate the safety and efficacy of clopidogrel + aspirin for secondary prevention of stroke, have been published. The efficacy of any antiplatelet therapy, including aspirin, is modest when it is used as monotherapy, and combination therapy with 2 antiplatelet agents has shown promise in reducing the risk for secondary stroke in patients who have had a previous transient ischemic attack (TIA) or ischemic stroke. However, unlike the Second European Stroke Prevention Study (ESPS-2), which demonstrated a significant reduction in risk for secondary stroke with aspirin + extended-release dipyridamole versus aspirin alone the results of the MATCH trial indicated that the reduction in risk achieved by adding aspirin to clopidogrel is not significantly greater than that achieved with clopidogrel alone. Furthermore, a significant increase in life-threatening bleeding complications was associated with the combination of clopidogrel + aspirin. Given these findings, clopidogrel + aspirin cannot be recommended at this time for the secondary prevention of stroke in patients who have had a previous ischemic stroke or TIA.     

Effect of atorvastatin and pravastatin on platelet inhibition by aspirin and clopidogrel treatment in patients with coronary stent thrombosis

We sought to determine a potential interaction between statins and antiplatelet therapy with aspirin and clopidogrel. Previous laboratory studies have shown a possible drug-drug interaction of statins metabolized by cytochrome P450 3A4 and clopidogrel (prodrug metabolized by cytochrome P450 3A4), resulting in an impaired inhibitory effect of clopidogrel on platelet aggregation. However, conclusive prospective data assessing this potentially relevant interaction are lacking. In 73 patients, 23 with previous coronary stent thrombosis (ST) (ST group) and 50 without coronary ST (control group), platelet aggregation was measured 3 times in monthly intervals using light transmission aggregometry (adenosine diphosphate [ADP] and arachidonic acid induction). Measurements were carried out with aspirin monotherapy (100 mg/day), dual antiplatelet therapy with aspirin plus clopidogrel (75 mg/day), and additional treatment of 20 mg/day of atorvastatin or 40 mg/day of pravastatin. ADP (5 and 20 micromol)-induced platelet aggregation was significantly decreased with clopidogrel (p <0.001) but remained stable under additional treatment with atorvastatin or pravastatin in the 2 groups. Patients with previous ST showed a higher ADP-induced aggregation level than control subjects. This difference was not influenced by clopidogrel or statin treatment. In conclusion, patients with previous ST show a higher aggregation level than control subjects independent of statin treatment. Atorvastatin and pravastatin do not interfere with the antiaggregatory effect of aspirin and clopidogrel. In conclusion, drug-drug interaction between dual antiplatelet therapy and atorvastatin or pravastatin seems not to be associated with ST.     

血液内溶血磷脂酸浓度与氯吡格雷治疗短暂性脑缺血发作疗效的关系

目的探讨血液内溶血磷脂酸(lysophosphatidic acid,LPA)浓度与氯吡格雷治疗短暂性脑缺血发作(transi-ent ischemic attack,TIA)疗效的关系。方法选择TIA患者77例,根据血液内LPA浓度分为LPA增高组(>3.2μmol/L,49例)和LPA正常组(≤3.2μmol/L,28例),用氯吡格雷75 mg/d进行治疗,随访1个月,观察TIA患者的发作频率以及发展成为脑梗死的发生率。结果 LPA增高组患者治疗前和治疗后LPA浓度明显高于LPA正常组,LPA增高组患者治疗后LPA浓度较治疗前明显降低(P<0.05)。经过1个月的氟吡格雷治疗,LPA增高组患者中,1个月内平均发作(1.53±0.34)次,共有8例发展成为脑梗死,发生率为16.3%,而LPA正常组患者中,1个月内平均发作(2.17±0.52)次,有7例发展成为脑梗死,发生率为25.0%。结论氯吡格雷治疗高血浓度LPA的TIA患者疗效优于正常血浓度LPA的TIA患者。     

Antithrombotic secondary prevention after stroke

Opinion statement In patients with transient ischemic attack (TIA) or ischemic stroke of noncardiac origin, antiplatelet drugs are able to decrease the risk of stroke by 11% to 15%, and decrease the risk of stroke, myocardial infarction (MI), and vascular death by 15% to 22%. Aspirin leads to a moderate but significant reduction of stroke, MI, and vascular death in patients with TIA and ischemic stroke. Low doses are as effective as high doses, but are better tolerated in terms of gastrointestinal side effects. The recommended aspirin dose, therefore, is between 50 and 325 mg. Bleeding complications are not dose-dependent, and also occur with the lowest doses. The combination of aspirin (25 mg twice daily) with slow-release dipyridamole (200 mg twice daily) is superior compared with aspirin alone for stroke prevention. Ticlopidine is effective in secondary stroke prevention in patients with TIA and stroke. For some end points, it is superior to aspirin. Due to its side-effect profile (neutropenia, thrombotic thrombocytopenic purpura [TTP]), ticlopidine should be given to patients who are intolerant of aspirin. Prospective trials have not indicated whether ticlopidine is suggested for patients who have recurrent cerebrovascular events while on aspirin. Clopidogrel has a better safety profile than ticlopidine. Although not investigated in patients with TIA, clopidogrel should also be effective in these patients assuming the same pathophysiology than in patients with stroke. Clopidogrel is second-line treatment in patients intolerant for aspirin, and first-line treatment for patients with stroke and peripheral arterial disease or MI. A frequent clinical problem is patients who are already on aspirin because of coronary heart disease or a prior cerebral ischemic event, and then suffer a first or recurrent TIA or stroke. No single clinical trial has investigated this problem. Therefore, recommendations are not evidence-based. Possible strategies include the following: continue aspirin, add dipyridamole, add clopidogrel, switch to ticlopidine or clopidogrel, or switch to anticoagulation with an International Normalized Ratio (INR) of 2.0 to 3.0. The combination of low-dose warfarin and aspirin was never studied in the secondary prevention of stroke. In patients with a cardiac source of embolism, anticoagulation is recommended with an INR of 2.0 to 3.0. At the present time, anticoagulation with an INR between 3.0 and 4.5 cannot be recommended for patients with noncardiac TIA or stroke. Anticoagulation with an INR between 3.0 and 4.5 carries a high bleeding risk. Whether anticoagulation with lower INR is safe and effective is not yet known. Treatment of vascular risk factors should also be performed in secondary stroke prevention.     

冠状动脉介入术后抗血小板治疗联合不同质子泵抑制剂对消化道出血的预防作用和心血管事件的影响

目的观察老年冠心病患者冠状动脉介入（PCI）术后氯吡格雷＋阿司匹林治疗与不同质子泵抑制剂联用在预防消化道出血及对血小板聚集率（PAR）和心血管事件发生情况的影响。方法选择符合入选条件的280例患者,在氯吡格雷十阿司匹林的基础上,随机分为5组,A组：对照组;B组：奥美拉唑20mg bid;C组：雷贝拉唑10mg bid;D组：兰索拉唑30mg qd;E组：埃索美拉唑20mg bid。治疗期间通过观察呕血、黑便、上腹不适或腹痛和反酸、烧心症状,行便隐血试验,胃镜检查,确定消化道损伤发生;同时观察心血管不良事件发生,并检测PAR。患者出院后门诊随访12个月。结果A、B、C、D、E组消化道损伤的发生率分别为28．85％、12．28％、10．53％、10．34％、8．93％;A组中出现3例消化道大出血,B、C、D、E组中均未出现;B、C、D、E四组与A组比较差异有统计学意义（P〈0．05）,B、C、D、E组之间无统计学差异。A、B、C、D、E组心血管事件发生率分别为5．77％、14．04％、7．02％、8．62％、8．93％;PAR分别为22％±7％、34％±11％、27％±6％、26％±7％、23％±6％,B组心血管事件发生率与PAR明显升高。结论PCI术后,氯吡格雷＋阿司匹林治疗与质子泵抑制剂联用可明显降低患者消化道出血的发生,奥美拉唑与其联用能明显提高血小板聚集率,降低抗血小板疗效,增加心脑血管事件的发生率,其他质子泵抑制剂对其抗血小板疗效无明显影响。