缺血性卒中二级预防中的抗血小板治疗

抗血小板治疗是缺血性卒中二级预防的重要措施之一。在缺血性卒中二级预防中,阿司匹林仍然是最常用的抗血小板药。氯吡格雷的疗效优于阿司匹林,但因其价格昂贵,目前仅在阿司匹林不能耐受或阿司匹林无效者中使用。联合用药只推荐缓释型双嘧达莫加小剂量阿司匹林。     

抗血小板药在缺血性卒中防治中的作用

抗血小板药在缺血性卒中防治中的作用已得到公认。阿司匹林可在缺血性卒中发病24～48h内应用，并可用于缺血性卒中的二级预防。阿司匹林抵抗人群或对阿司匹林不能耐受者，可改用其他抗血小板药。文章主要探讨抗血小板药的临床应用、最佳剂量以及抗血小板药与其他干预手段的联合应用。     

抗血小板药在缺血性卒中防治中的作用

抗血小板药在缺血性卒中防治中的作用已得到公认。阿司匹林可在缺血性卒中发病 2 4～ 4 8h内应用 ,并可用于缺血性卒中的二级预防。阿司匹林抵抗人群或对阿司匹林不能耐受者 ,可改用其他抗血小板药。文章主要探讨抗血小板药的临床应用、最佳剂量以及抗血小板药与其他干预手段的联合应用。     

抗血小板药物治疗缺血性脑血管病的合理应用

抗血小板疗法是缺血性脑血管病治疗中的主要策略,研究证据最多.本文介绍了常用抗血小板药物的作用机制以及指南性建议和临床试验证据.目前尚无足够的证据推荐使用静脉抗血小板制剂.阿司匹林是惟一经过循证医学证明有效并用于急性缺血性卒中的抗血小板药物.在卒中二级预防中,推荐阿司匹林,氯吡格雷或阿司匹林与缓释双嘧达莫,后者的联合应用是目前惟一证明有附加受益的双重抗血小板治疗.     

阿司匹林对缺血性卒中二级预防的大型临床试验

阿司匹林是目前世界上应用最多的抗血小板聚集药，广泛应用于心脑血管病的防治。文章介绍了阿司匹林对缺血性卒中二级预防较有影响的大型临床试验及其汇总分析。     

阿司匹林对缺血性卒中二级预防的大型临床试验

阿司匹林是目前世界上应用最多的抗血小板聚集药,广泛应用于心脑血管病的防治。文章介绍了阿司匹林对缺血性卒中二级预防较有影响的大型临床试验及其汇总分析。     

抗磷脂抗体综合征与缺血性卒中治疗的争论

近年来，人们逐渐认识到抗磷脂抗体综合征在缺血性卒中发病中具有一定的作用，且缺血性卒中常反复发作，因而抗磷脂抗体综合征的治疗对缺血性卒中的一级和二级预防愈显重要。但对以华法林为代表的抗凝治疗和以阿司匹林为代表的抗血小板治疗，应当如何评价其疗效，目前的资料表明尚存在一些异议。文章就此做了总结。     

阿司匹林与氯吡格雷联用对缺血性卒中的二级预防无明显益处

抗血小板治疗是非心源性栓塞性缺血性卒中后二级预防的标准治疗方法。法国巴黎Sainte-Anne 医院神经科Calvet等进行了一项对照研究，旨在高危患者近期缺血性卒中或短暂性脑缺血发作后的二级预防中对联合应用阿司匹林（75mg）和氯吡格雷（75mg）与单用氯吡格雷（75mg）进行比较。     

阿司匹林抵抗与缺血性卒中

卒中已成为中国居民的第一位死亡原因。作为缺血性卒中一级和二级预防的基石，阿司匹林在一定程度上能预防缺血性卒中的发病和复发。然而，部分患者在规律服用阿司匹林后仍然发生血管事件，或血小板聚集率较高，这种现象被称为“阿司匹林抵抗”或“阿司匹林低反应性”。文章对缺血性卒中患者阿司匹林抵抗的发生情况、检测方法和处理措施进行了综述。     

糖化白蛋白与阿司匹林抵抗的关系

正随着全球步入老龄化社会,脑梗死患病率不断增加,心脑血管疾病已成为导致人类死亡的主要病因~([1])。阿司匹林作为抗血小板聚集药物,可以降低缺血性卒中的风险,是卒中一级预防及二级预防的基石~([2])。随着阿司匹林临床应用的扩展,研究发现,阿司匹林在人群中存在个体差异,5.5%~61%的卒中患者对阿司匹林的抗血小板聚集治疗不敏感,即为阿司匹林抵抗~([3])。目前阿司匹林抵抗发生的机制尚不清楚,潜在因素包括患者的顺应性、临床特征、     

Preventing stroke in patients with atrial fibrillation: current treatments and new concepts

Atrial fibrillation (AF) is common, and it increases the risk of stroke. Placebo-controlled trials consistently showed that warfarin reduces the risk of stroke by two thirds, and a meta-analysis of trials of aspirin show a one-fifth reduction. Meta-analysis of trials directly comparing warfarin and aspirin shows that warfarin reduces the risk of stroke compared with aspirin by about one third. Major advisory bodies recommend risk stratification of patients with AF and prophylactic therapy with warfarin for patients at higher risk. There are several problems with warfarin therapy, which have resulted in a widely documented underuse. These problems include a narrow therapeutic window, marked variability in pharmacokinetics, and contraindications. There are new promising approaches to stroke prevention in AF. One of these is combination antiplatelet therapy. In a large randomized trial, the combination of dipyridamole and aspirin has been shown to have additive benefits against stroke. The combination of clopidogrel and aspirin results in additive benefits against vascular events, with only a modest increase in bleeding. A trial of combined antiplatelet therapy in AF is warranted. Occlusion of the left atrial appendage, either with a transvenous device or with surgery, is another strategy that is being explored. A direct thrombin inhibitor, ximelagatran, has been shown to have an excellent pharmacokinetic profile and is being developed as an oral agent for stroke prevention in AF, and it will not need regular monitoring. (Am Heart J 2003;145:418-23.)     

Indications of combined vitamin K antagonists and aspirin therapy

Based on their mode of action, it is reasonable to expect that the combination therapy of aspirin and a vitamin K antagonist (VKA) may be more beneficial in preventing (athero) thrombotic complications in high-risk patients for cardiovascular events. However, there is no consensus about additional aspirin use in the most common indications for VKA or the use of VKAs to be added to the most common aspirin indications. The variation in clinical outcomes and bleeding complications suggests that extrapolating from one indication to another may not be appropriate. So far, decisions about the combined use of aspirin and VKA are individualized in the absence of adequate data. Only in patients with mechanical heart valves the benefits and safety of combining aspirin with VKA therapy seems obvious. In patients with peripheral artery disease no beneficial effect was noted for the combination therapy, perhaps with an exception of those with graft failure. For all other clinical situations, this is unclear and should be avoided.     

The thienopyridines

Platelet adhesion, activation, and aggregation are key processes in the pathogenesis of coronary disease. Inhibition of these processes forms the cornerstone of therapy for coronary artery disease and particularly of acute coronary syndromes (ACS). Aspirin was the only available antiplatelet therapy for over 100 years, and it improves clinical outcome in a wide range of clinical situations. However, aspirin only inhibits platelet activation mediated by thromboxane A2, allowing platelet activation to occur through innumerable other pathways. As a result, adverse ischemic events are common when aspirin alone is used for the treatment of coronary disease, including ACS, during coronary interventions (particularly during stent implantation), and following coronary vascular brachytherapy (VBT). In these clinical situations, the presence of either thrombus, deep injury to the vessel wall, or delayed vascular reendothelialization leads to intense and often prolonged platelet activation, overwhelming the relatively weak effects of aspirin. The development of the thienopyridines, a class of antiplatelet drugs that reduce adenosine diphosphate-(ADP) mediated platelet activation, has significantly improved clinical outcomes in many coronary conditions. Widespread use of ticlopidine, the first available thienopyridine, was limited by frequent side-effects, including life-threatening neutropenia and thrombotic thrombocytopenic purpura. Following the introduction of clopidogrel, a thienopyridine with an excellent safety profile, dual antiplatelet therapy with aspirin and clopidogrel has become standard therapy following coronary stent implantation and coronary VBT. In patients presenting with ACS, the addition of clopidogrel to aspirin has now been proven to reduce ischemic events. The most important limitation of dual antiplatelet therapy is the increased bleeding risk as compared with aspirin alone, particularly in patients undergoing coronary artery bypass grafting during the index hospitalization. However, for many patients with ACS, combination therapy is appropriate.     

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.     

Optimal platelet inhibition therapy in unstable angina pectoris and after coronary interventions

ASPIRIN AND HEPARIN: In several studies aspirin has been found to be very effective in unstable angina pectoris reducing fatal and non-fatal myocardial infarction by 50-70%. Unfortunately the optimal dose of aspirin is still an open question. Whereas heparin alone shows only a weak effectiveness the combination of aspirin and heparin is superior to aspirin alone and is still the basis of antithrombotic therapy in unstable angina. TICLOPIDINE AND CLOPIDOGREL: Experience with thienopyridine derivatives in unstable angina is limited. Ticlopidine has been found to be superior to aspirin alone. Data with the combination of clopidogrel and aspirin should be available soon. THERAPEUTIC RECOMMENDATION AFTER CORONARY INTERVENTION: Both, ticlopidine and clopidogrel have been found to be very effective in preventing coronary-stent thrombosis when combined with aspirin. Meanwhile ticlopidine has been widely substituted by clopidogrel due to the better safety profile of the latter one. 75 mg clopidogrel daily combined with aspirin is recommended for at least 4 weeks after coronary stenting.     

Department of Veterans Affairs Cooperative Studies Program Clinical Trial comparing combined warfarin and aspirin with aspirin alone in survivors of acute myocardial infarction: primary results of the CHAMP study

BACKGROUND: Both aspirin and warfarin when used alone are effective in the secondary prevention of vascular events and death after acute myocardial infarction. We tested the hypothesis that aspirin and warfarin therapy, when combined, would be more effective than aspirin monotherapy. Methods and Results- We conducted a randomized open-label study to compare the efficacy of warfarin (target international normalized ratio 1.5 to 2.5 IU) plus aspirin (81 mg daily) with the efficacy of aspirin monotherapy (162 mg daily) in reducing the total mortality in 5059 patients enrolled within 14 days of infarction and followed for a median of 2.7 years. Secondary end points included recurrent myocardial infarction, stroke, and major hemorrhage. Four hundred thirty-eight (17.3%) of 2537 patients assigned to the aspirin group and 444 (17.6%) of 2522 patients assigned to the combination group died (log-rank P=0.76). Recurrent myocardial infarction occurred in 333 patients (13.1%) taking aspirin and in 336 patients (13.3%) taking combination therapy (log-rank P=0.78). Stroke occurred in 89 patients (3.5%) taking aspirin and in 79 patients (3.1%) taking combination therapy (log-rank P=0.52). Major bleeding occurred more frequently in the combination therapy group than in the aspirin group (1.28 versus 0.72 events per 100 person years of follow-up, respectively; P<0.001). There were 14 individuals with intracranial bleeds in both the aspirin and combination therapy groups. CONCLUSIONS: In post-myocardial infarction patients, warfarin therapy (at a mean international normalized ratio of 1.8) combined with low-dose aspirin did not provide a clinical benefit beyond that achievable with aspirin monotherapy.     

Combination antithrombotic therapy with antiplatelet agents and anticoagulants for patients with atherosclerotic heart disease

We reviewed the efficacy and safety of combination antithrombotic therapy with aspirin plus warfarin versus aspirin alone in patients with atherosclerotic heart disease. We performed a comprehensive MEDLINE search of English-language reports published between 1966 and 2002 and search of references and relevant papers. Only clinical research studies on primary or secondary prevention of cardiovascular events in patients at high risk for coronary artery disease or patients experiencing unstable angina or myocardial infarction were included. Despite daily aspirin treatment, many patients break through aspirin treatment and experience cardiovascular events. Individuals at high risk for coronary disease or with established disease benefit from combination therapy with aspirin plus warfarin, if compliance with warfarin is greater than 70% and the target international normalized ratio (INR) of 2.0-2.5 is achieved. Combination therapy within these parameters leads to a 29-45% reduction in the risk of death, reinfarction and/or ischemic stroke. There is a significant increase in the rate of minor and a slight increase in the rate of major bleeding with combination therapy. Other potential indications for combination therapy include myocardial infarction associated with acute left ventricular aneurysm or significant left ventricular systolic dysfunction. In spite of reluctance to use oral anticoagulants, several large, randomized clinical trials support combination therapy with aspirin plus warfarin (INR, 2.0-2.5) in high-risk patients with atherosclerotic heart disease. Combination therapy increases the risk of minor and major bleeding, but not intracranial bleeding.     

The effect of clopidogrel, aspirin and both antiplatelet drugs on platelet function in patients with peripheral arterial disease

Peripheral arterial disease (PAD) is associated with platelet hyperactivity. Aspirin and clopidogrel, two platelet inhibitors, act by different mechanisms. Aspirin inhibits thromboxane A2 synthesis and clopidogrel acts on the P2Y12 platelet ADP receptor. We evaluated the effect of clopidogrel (75 mg/day), aspirin (75 mg/day) and then both drugs on several platelet function indices in patients with PAD (n = 20). There was a significant (P = 0.0001) decrease in ADP-induced aggregation, after clopidogrel but not after taking aspirin. Clopidogrel plus aspirin significantly decreased spontaneous platelet aggregation (SPA) (P = 0.01 to P = 0.002) but SPA was not significantly altered by either aspirin or clopidogrel monotherapy. Similarly, monotherapy did not inhibit serotonin (5HT)-induced aggregation but there was a sigificant inhibition (P = 0.03 to P < 0.02) after combination therapy. ADP (0.8 microM)-induced platelet shape change (PSC) was significantly inhibited by clopidogrel (P = 0.004) or aspirin (P = 0.01). This was also true for 5HT-induced PSC (clopidogrel, P = 0.01; aspirin, P = 0.03). Soluble P-selectin decreased significantly (from 32 +/- 24 to 25 +/- 17 ng/ml, P = 0.04) with combination therapy. Plasma platelet-derived growth factor and intraplatelet 5HT levels were not altered by combination therapy. In PAD, clopidogrel is a more potent inhibitor of ADP-induced platelet activation than aspirin; combination therapy is more effective than clopidogrel or aspirin monotherapy. These potentially clinically relevant findings should be evaluated in appropriately designed trials.     

Hypersensitivity to warfarin in a patient with a mechanical aortic prosthesis.

The case of a patient with a prosthetic aortic valve and warfarin hypersensitivity is presented. On rechallenging the patient with warfarin, a spongiotic dermatitis with heavy superficial perivascular lymphocytic infiltrates with eosinophils was seen. The patient was finally discharged on aspirin therapy alone and is doing well to date. Warfarin hypersensitivity is rare, and only incidental reports exist regarding its incidence and management. It is conceivable that newer antiplatelet agents, whether alone or in combination with aspirin, will provide better control of thromboembolic events in patients with warfarin intolerance.