Neil E. Schwartz, MD, PhD Stanford Stroke Center, Department of Neurology and Neurological Sciences, Stanford University, 701 Welch Road, #B325, Palo Alto, CA 94304, USA.
Curr Treat Options Neurol. 2007 Nov;9(6):442-50. doi: 10.1007/s11940-007-0045-y.
Antiplatelet medications are the agents of choice for secondary prevention of noncardioembolic ischemic strokes. Multiple clinical trials have proven their reliable albeit modest clinical benefits and relatively good safety profile. The most commonly recommended antiplatelet agents for secondary stroke prevention in North America and Europe are aspirin, clopidogrel, and the combination of aspirin and extended-release dipyridamole. Because of the multiple pharmacologic mechanisms available for platelet inhibition, combination antiplatelet agents have the potential for synergistic effects. However, combinations of antithrombotic agents do not necessarily improve clinical efficacy and are typically associated with increased toxicity. Clopidogrel and aspirin have been used in combination in patients with diverse arterial vascular diseases. Combination antiplatelet therapy with clopidogrel and aspirin has established clinical benefits, particularly in coronary disease and in patients who have undergone coronary stenting. Although it is tempting to extrapolate the benefits of clopidogrel and aspirin to the setting of secondary stroke prevention, recent clinical trials have failed to document significant clinical benefits in cerebrovascular patients. This failure has occurred because of a lack of significant efficacy for prevention of vascular events and a substantial increase in bleeding risk. Therefore, the clopidogrel and aspirin combination is not recommended for recurrent stroke prevention. In general, when clopidogrel is used for cerebrovascular patients, the addition of aspirin should be avoided unless there is a specific cardiac indication such as recent acute coronary syndrome or a coronary stent. The combination of aspirin and extended-release dipyridamole is supported by Class I data from two large studies demonstrating superiority over aspirin alone for recurrent stroke prevention. Although dual antiplatelet therapy with clopidogrel and aspirin has never been directly compared with the combination of aspirin and extended-release dipyridamole, clinical trial results favor the latter for secondary stroke prevention. Currently, there are no data for primary stroke prevention with dual antiplatelet agents regarding aspirin and extended-release dipyridamole. Limited data from the recent Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization Management and Avoidance (CHARISMA) trial indicate that the combination of clopidogrel and aspirin may be harmful, compared with aspirin alone.
抗血小板药物是预防非心源性缺血性脑卒中二级复发的首选药物。多项临床试验已经证实了它们可靠的、尽管效果有限但安全性良好的临床获益。在北美和欧洲，最常推荐用于二级卒中预防的抗血小板药物是阿司匹林、氯吡格雷和阿司匹林与缓释双嘧达莫的联合用药。由于血小板抑制的多种药理机制，联合抗血小板药物可能具有协同作用。然而，抗血栓药物的联合使用并不一定能提高临床疗效，而且通常与毒性增加有关。氯吡格雷和阿司匹林已被用于治疗多种动脉血管疾病的患者。氯吡格雷和阿司匹林联合抗血小板治疗已确立了临床获益，特别是在冠心病和接受冠状动脉支架置入术的患者中。尽管将氯吡格雷和阿司匹林的获益推断到二级卒中预防的情况下具有吸引力，但最近的临床试验未能证明脑血管病患者有显著的临床获益。这一失败是由于预防血管事件的效果不显著和出血风险显著增加所致。因此，不建议将氯吡格雷和阿司匹林联合用于复发性卒中预防。一般来说，当氯吡格雷用于脑血管病患者时，除非有特定的心脏指征，如近期急性冠脉综合征或冠状动脉支架置入，否则应避免加用阿司匹林。两项大型研究的 I 类数据支持阿司匹林与缓释双嘧达莫联合应用，表明其在预防复发性卒中方面优于单独应用阿司匹林。虽然氯吡格雷和阿司匹林双联抗血小板治疗从未与阿司匹林与缓释双嘧达莫的联合应用直接比较，但临床试验结果倾向于后者用于二级卒中预防。目前，尚无关于阿司匹林和缓释双嘧达莫双联抗血小板药物用于一级卒中预防的数据。最近氯吡格雷用于高动脉血栓形成风险和缺血稳定管理及避免（CHARISMA）试验的有限数据表明，与单独应用阿司匹林相比，氯吡格雷和阿司匹林联合应用可能有害。
