Internal Medicine and CARIM School for Cardiovascular Research, Maastricht University Medical Center, Maastricht, The Netherlands.
Thrombosis Expertise Center, Heart+ Cardiovascular Center, and Department of Biochemistry, Maastricht University Medical Center, Maastricht, The Netherlands.
Handb Exp Pharmacol. 2022;270:103-130. doi: 10.1007/164_2020_357.
Atherosclerosis is a multifactorial vascular disease that develops in the course of a lifetime. Numerous risk factors for atherosclerosis have been identified, mostly inflicting pro-inflammatory effects. Vessel injury, such as occurring during erosion or rupture of atherosclerotic lesions triggers blood coagulation, in attempt to maintain hemostasis (protect against bleeding). However, thrombo-inflammatory mechanisms may drive blood coagulation such that thrombosis develops, the key process underlying myocardial infarction and ischemic stroke (not due to embolization from the heart). In the blood coagulation system, platelets and coagulation proteins are both essential elements. Hyperreactivity of blood coagulation aggravates atherosclerosis in preclinical models. Pharmacologic inhibition of blood coagulation, either with platelet inhibitors, or better documented with anticoagulants, or both, limits the risk of thrombosis and may potentially reverse atherosclerosis burden, although the latter evidence is still based on animal experimentation.Patients at risk of atherothrombotic complications should receive a single antiplatelet agent (acetylsalicylic acid, ASA, or clopidogrel); those who survived an atherothrombotic event will be prescribed temporary dual antiplatelet therapy (ASA plus a P2Y12 inhibitor) in case of myocardial infarction (6-12 months), or stroke (<6 weeks), followed by a single antiplatelet agent indefinitely. High risk for thrombosis patients (such as those with peripheral artery disease) benefit from a combination of an anticoagulant and ASA. The price of gained efficacy is always increased risk of (major) bleeding; while tailoring therapy to individual needs may limit the risks to some extent, new generations of agents that target less critical elements of hemostasis and coagulation mechanisms are needed to maintain efficacy while reducing bleeding risks.
动脉粥样硬化是一种多因素的血管疾病，它在人的一生中发展。已经确定了许多动脉粥样硬化的危险因素，其中大多数会产生促炎作用。血管损伤，如在动脉粥样硬化病变的侵蚀或破裂过程中发生，会触发血液凝固，以试图维持止血（防止出血）。然而，血栓炎症机制可能会驱动血液凝固，导致血栓形成，这是心肌梗死和缺血性中风（不是由于心脏栓塞）的关键过程。在凝血系统中，血小板和凝血蛋白都是必不可少的元素。在临床前模型中，凝血的高反应性会加重动脉粥样硬化。血小板抑制剂或抗凝剂（或两者兼有）的药理学抑制可限制血栓形成的风险，并可能潜在地逆转动脉粥样硬化负担，尽管后者的证据仍基于动物实验。有发生动脉粥样硬化血栓并发症风险的患者应使用单一抗血小板药物（乙酰水杨酸，ASA 或氯吡格雷）；那些在动脉粥样硬化血栓事件中幸存的患者将在心肌梗死（6-12 个月）或中风（<6 周）后接受临时双联抗血小板治疗（ASA 加 P2Y12 抑制剂），随后无限期使用单一抗血小板药物。高血栓形成风险患者（如外周动脉疾病患者）受益于抗凝剂和 ASA 的联合治疗。疗效增加的代价始终是（主要）出血风险增加；虽然根据个体需求定制治疗在一定程度上可以限制风险，但需要新一代靶向止血和凝血机制中不太关键元素的药物，以在降低出血风险的同时保持疗效。
