Department of Cardiology, Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, Aarhus, Denmark.
Curr Vasc Pharmacol. 2012 Jul;10(4):494-505. doi: 10.2174/157016112800812818.
Platelets are key players in arterial thrombosis, and oral antiplatelet therapy is a cornerstone in the treatment and prevention of cardiovascular events. However, although currently approved antiplatelet drugs have proved successful in reducing cardiovascular events, platelet-dependent thrombosis remains an important cause of morbidity and mortality in patients with coronary artery disease. It is well-known that patients with diabetes mellitus (DM) have an increased risk of cardiovascular events and, therefore, understanding the mechanism of action and safety profile of antiplatelet drugs in this high-risk population is of particular interest. There is considerable inter-individual variation in the efficacy of established antiplatelet drugs, and high on-treatment platelet reactivity is associated with an increased risk of cardiovascular events, thus prompting the search for novel drugs against platelet-dependent thrombosis. New antiplatelet treatment strategies include drugs with more efficient and reversible platelet inhibition. This review discusses selective inhibitors of the platelet cyclooxygenase enzyme, thienopyridine and non-thienopyridine inhibitors of the platelet adenosine diphosphate receptor, phosphodiesterase inhibitors, and protease-activated receptor antagonists. An overview of currently available antiplatelet drugs is provided, focusing on benefits and limitations in patients with DM. Furthermore, the rationale for new oral antiplatelet drugs under development is discussed with particular focus on the potential role of these drugs to improve cardiovascular outcomes in patients with DM.
血小板是动脉血栓形成的关键因素,口服抗血小板治疗是治疗和预防心血管事件的基石。然而,尽管目前批准的抗血小板药物已被证明能有效减少心血管事件,但血小板依赖性血栓形成仍然是冠心病患者发病率和死亡率的重要原因。众所周知,糖尿病(DM)患者发生心血管事件的风险增加,因此,了解抗血小板药物在这一高危人群中的作用机制和安全性特征尤为重要。已确立的抗血小板药物的疗效存在相当大的个体差异,治疗中血小板反应性高与心血管事件风险增加相关,因此促使人们寻找针对血小板依赖性血栓形成的新型药物。新的抗血小板治疗策略包括具有更有效和可逆的血小板抑制作用的药物。本文讨论了血小板环氧化酶酶的选择性抑制剂、血小板二磷酸腺苷受体的噻吩吡啶和非噻吩吡啶抑制剂、磷酸二酯酶抑制剂和蛋白酶激活受体拮抗剂。概述了目前可用的抗血小板药物,重点关注这些药物在 DM 患者中的获益和局限性。此外,还讨论了正在开发的新型口服抗血小板药物的原理,特别关注这些药物在改善 DM 患者心血管结局方面的潜在作用。