Easton J Donald
Department of Neurology, Brown University, Providence, RI, USA.
Cerebrovasc Dis. 2003;16 Suppl 1:20-6. doi: 10.1159/000069937.
Antiplatelet drugs have been shown to prevent a range of atherothrombotic events, including transient ischaemic attack (TIA) and ischaemic stroke. Clopidogrel and ticlopidine are adenosine diphosphate (ADP)-receptor antagonists that inhibit ADP-induced fibrinogen binding to platelets, a necessary step in the platelet aggregation process. The Antithrombotic Trialists' Collaboration recently published a major meta-analysis that assessed the effect of antiplatelet therapy in patients with various manifestations of atherosclerosis. In total, this analysis included 135,000 patients in comparisons of antiplatelet agents versus control and 77,000 patients in comparisons of different antiplatelet regimens. This meta-analysis found that overall, antiplatelet therapy reduces the combined odds of stroke, myocardial infarction (MI) or vascular death by 22%, and that antiplatelet agents reduce the odds of a non-fatal stroke by 25% over a wide range of patients with or without a history of cerebrovascular disease. In the CAPRIE trial of clopidogrel versus acetylsalicylic acid (ASA), there was a 10% odds reduction for stroke, MI or vascular death in favour of clopidogrel (p = 0.03). In a meta-analysis performed by the Cochrane Stroke Group, ADP-receptor antagonist therapy significantly reduced the odds of a serious vascular event (stroke, MI or vascular death) by 9% (2p = 0.01) and of any stroke by 12%. The safety/tolerability profile of clopidogrel was superior to that of ticlopidine, and at least as good as that of ASA. In CURE, a long-term benefit was observed with the use of clopidogrel on top of standard therapy (including ASA in all patients), with a 20% relative risk reduction for the primary endpoint of cardiovascular death, MI or stroke (p < 0.001) in patients with unstable angina and non-Q-wave MI. A consistent benefit was seen across all patient subgroups, including patients with a previous history of stroke. More recently, CREDO has demonstrated the incremental benefit of prolonged use of clopidogrel on top of ASA in patients undergoing elective PCI, with a 27% reduction in the combined risk of death, MI or stroke after 12 months of therapy (p = 0.02) and a 25% reduction in stroke over the same time period. The MATCH trial is currently being conducted to test the hypothesis that long-term administration of clopidogrel on top of ASA is superior to clopidogrel alone for the reduction of major ischaemic events in patients with recent TIA or ischaemic stroke who are at high risk of atherothrombotic recurrence. Further trials of clopidogrel on top of standard therapy (including ASA) are planned in neurology; these include SPS3, in patients with small subcortical strokes, and ATARI, in patients who have recently recovered from a TIA.
抗血小板药物已被证明可预防一系列动脉粥样硬化血栓形成事件，包括短暂性脑缺血发作（TIA）和缺血性中风。氯吡格雷和噻氯匹定是二磷酸腺苷（ADP）受体拮抗剂，可抑制ADP诱导的纤维蛋白原与血小板结合，这是血小板聚集过程中的必要步骤。抗栓试验协作组最近发表了一项重要的荟萃分析，评估了抗血小板治疗对各种动脉粥样硬化表现患者的疗效。总体而言，该分析在抗血小板药物与对照组的比较中纳入了135000名患者，在不同抗血小板治疗方案的比较中纳入了77000名患者。这项荟萃分析发现，总体而言，抗血小板治疗可使中风、心肌梗死（MI）或血管性死亡的综合几率降低22%，并且抗血小板药物在广泛的有或没有脑血管疾病病史的患者中可使非致命性中风的几率降低25%。在氯吡格雷与阿司匹林（ASA）的CAPRIE试验中，中风、MI或血管性死亡的几率降低了10%，氯吡格雷更具优势（p = 0.03）。在Cochrane中风小组进行的一项荟萃分析中，ADP受体拮抗剂治疗可使严重血管事件（中风、MI或血管性死亡）的几率显著降低9%（2p = 0.01），使任何中风的几率降低12%。氯吡格雷的安全性/耐受性优于噻氯匹定，至少与ASA相当。在CURE研究中，在标准治疗（包括所有患者均使用ASA）基础上加用氯吡格雷可观察到长期获益，不稳定型心绞痛和非Q波MI患者心血管死亡、MI或中风的主要终点相对风险降低20%（p < 0.001）。在所有患者亚组中均观察到一致的获益，包括有中风病史的患者。最近，CREDO研究表明，在接受择期PCI的患者中，在ASA基础上延长使用氯吡格雷有额外获益，治疗12个月后死亡、MI或中风的联合风险降低27%（p = 0.02），同期中风风险降低25%。MATCH试验目前正在进行，以检验以下假设：对于近期有TIA或缺血性中风且动脉粥样硬化血栓形成复发风险高的患者，在ASA基础上长期服用氯吡格雷优于单独使用氯吡格雷，可降低主要缺血事件的发生风险。神经病学领域还计划进行更多在标准治疗（包括ASA）基础上加用氯吡格雷的试验；这些试验包括针对皮质下小中风患者的SPS3试验和针对近期从TIA恢复患者的ATARI试验。
