de Gaetano G, Cerletti C, Dejana E, Vermylen J
Drugs. 1986 Jun;31(6):517-49. doi: 10.2165/00003495-198631060-00004.
In this review, the major current problems related to the pharmacology and clinical use of antiplatelet drugs are discussed in relation to the physiopathology of the platelet-vessel wall interaction and arterial thrombus formation. Although platelet adhesion to injured vessels is a crucial step in thrombogenesis, none of the currently used antiaggregating drugs prevents this phenomenon. Why the normal endothelium does not react with platelets is not known. Thus we are unable to pharmacologically restore endothelial 'non-thrombogenicity' when lost by single or repeated injury. In contrast, more information is available on the mechanisms controlling and amplifying platelet activation by physiological stimuli (such as collagen and thrombin), and on their pharmacological modulation. The 3 main amplification loops involve arachidonic acid metabolism, ADP release and possibly the availability of a phospholipid platelet activating factor. These pathways are in turn activated by the phosphatidylinositol cycle. The most widely used antiaggregating drug is aspirin. It prevents the formation of arachidonic acid metabolites both in platelets and in vascular cells. The use of low-dose aspirin, thromboxane-synthase inhibitors, thromboxane receptor antagonists, epoprostenol (prostacyclin) and its stable analogues, and ticlopidine all appear to be promising pharmacological approaches, but none has so far been tested in clinical trials for thrombosis prevention. On the other hand, aspirin (in relatively large doses of 300 to 1500 mg daily), sulphinpyrazone and dipyridamole have been tested alone or in combination in the secondary prevention of thromboembolic complications. Aspirin has significantly reduced both the occurrence of myocardial infarction and mortality rate in patients with unstable angina and/or previous myocardial infarction; it has also proved beneficial in cerebrovascular disease. The beneficial effect of aspirin was dose-independent. In some of these trials aspirin was combined with either dipyridamole or sulphinpyrazone. When used alone, the latter compound has reduced sudden death or thromboembolic complications in patients with myocardial infarction. It remains to be established whether antiplatelet therapy may prevent or stop the progression of atherosclerosis.
在本综述中，结合血小板 - 血管壁相互作用及动脉血栓形成的生理病理学，讨论了抗血小板药物药理学及临床应用方面当前存在的主要问题。尽管血小板黏附于受损血管是血栓形成过程中的关键步骤，但目前使用的抗聚集药物均不能预防这一现象。正常内皮细胞为何不与血小板发生反应尚不清楚。因此，当因单次或反复损伤导致内皮细胞丧失“非血栓形成性”时，我们无法通过药物手段恢复其功能。相比之下，关于生理刺激（如胶原蛋白和凝血酶）控制和放大血小板活化的机制及其药理学调节，我们了解得更多。3个主要的放大环路涉及花生四烯酸代谢、ADP释放以及磷脂血小板活化因子的可用性。这些途径又由磷脂酰肌醇循环激活。使用最广泛的抗聚集药物是阿司匹林。它可防止血小板和血管细胞中花生四烯酸代谢产物的形成。使用低剂量阿司匹林、血栓素合成酶抑制剂、血栓素受体拮抗剂、依前列醇（前列环素）及其稳定类似物以及噻氯匹定，似乎都是很有前景的药理学方法，但目前尚无一种在预防血栓形成的临床试验中得到检验。另一方面，阿司匹林（每日剂量相对较大，为300至1500毫克）、磺吡酮和双嘧达莫已单独或联合用于血栓栓塞并发症的二级预防试验。阿司匹林显著降低了不稳定型心绞痛和/或既往心肌梗死患者心肌梗死的发生率和死亡率；在脑血管疾病中也已证明其有益作用。阿司匹林的有益作用与剂量无关。在其中一些试验中，阿司匹林与双嘧达莫或磺吡酮联合使用。单独使用时，后一种化合物降低了心肌梗死患者的猝死或血栓栓塞并发症发生率。抗血小板治疗是否可以预防或阻止动脉粥样硬化的进展仍有待确定。
