Diener Hans-Christoph, Ringleb Peter
*Department of Neurology, University of Essen, Hufelandstrasse 55, Essen 45122, Germany.
Curr Treat Options Neurol. 2001 Sep;3(5):451-462. doi: 10.1007/s11940-001-0033-6.
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 term 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 endpoints, it is superior to aspirin. Due to its side effect profile (neutropenia, thrombotic thrombocytopenic purpura ), 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 can not 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.
在短暂性脑缺血发作（TIA）或非心源性缺血性卒中患者中，抗血小板药物能够将卒中风险降低11%至15%，并将卒中、心肌梗死（MI）和血管性死亡风险降低15%至22%。阿司匹林可使TIA和缺血性卒中患者的卒中和MI及血管性死亡适度但显著减少。低剂量与高剂量同样有效，但在胃肠道副作用方面耐受性更好。因此，推荐的阿司匹林剂量为50至325毫克。出血并发症与剂量无关，最低剂量时也会发生。阿司匹林（每日两次，每次25毫克）与缓释双嘧达莫（每日两次，每次200毫克）联合用于预防卒中优于单用阿司匹林。噻氯匹定对TIA和卒中患者的二级卒中预防有效。对于某些终点而言，它优于阿司匹林。由于其副作用（中性粒细胞减少、血栓性血小板减少性紫癜），噻氯匹定应给予不耐受阿司匹林的患者。前瞻性试验未表明对于正在服用阿司匹林时发生复发性脑血管事件的患者是否建议使用噻氯匹定。氯吡格雷的安全性优于噻氯匹定。虽然未在TIA患者中进行研究，但假设其病理生理与卒中患者相同，氯吡格雷对这些患者也应有效。氯吡格雷是不耐受阿司匹林患者的二线治疗药物，是卒中、外周动脉疾病或MI患者的一线治疗药物。一个常见的临床问题是因冠心病或既往脑缺血事件已在服用阿司匹林的患者，随后发生首次或复发性TIA或卒中。尚无单一临床试验研究过这个问题。因此，相关建议并非基于证据。可能的策略如下：继续使用阿司匹林、加用双嘧达莫、加用氯吡格雷、换用噻氯匹定或氯吡格雷，或换用国际标准化比值（INR）为2.0至3.0的抗凝治疗。低剂量华法林与阿司匹林联合应用在卒中二级预防中从未被研究过。对于有心源性栓塞的患者，推荐INR为2.0至3.0的抗凝治疗。目前，对于非心源性TIA或卒中患者，不推荐INR在3.0至4.5之间的抗凝治疗。INR在3.0至4.5之间的抗凝治疗出血风险高。INR较低时的抗凝治疗是否安全有效尚不清楚。在卒中二级预防中也应治疗血管危险因素。
