Department of Pharmacy Practice, Creighton University School of Pharmacy and Health Professions, Omaha, Nebraska 68178, USA.
Pharmacotherapy. 2011 Oct;31(10):975-1016. doi: 10.1592/phco.31.10.975.
Abstract Thrombosis is an underlying cause of many cardiovascular disorders, and generation of thrombi in the arterial circulation can lead to unstable angina, myocardial infarction, or ischemic stroke. Antithrombotic therapy is widely used, with proven benefit to prevent ischemic stroke and thromboembolic events in patients with atrial fibrillation (AF) or to prevent further ischemic complications in patients with acute coronary syndrome (ACS). Traditional anticoagulants (including unfractionated heparin, low-molecular-weight heparin, and warfarin) and antiplatelet agents (including aspirin, clopidogrel, and prasugrel) are typically used for these indications. Limitations to their use include variable pharmacokinetic and pharmacodynamic profiles, inability to inhibit fibrin-bound thrombin, risk of heparin-induced thrombocytopenia, delayed onset of action, numerous drug interactions, need for substantial laboratory monitoring and dosage titrations, hyporesponsiveness or resistance, hypersensitivity, adverse events, and bleeding. To overcome some of the limitations of traditional agents, new antithrombotic agents under development are highly selective for specific coagulation factors blocking the synthesis of thrombin. Clinicians must have an understanding of the new anticoagulants to aid in the selection of appropriate therapies for patients. We describe the most relevant phases II and III clinical trials that evaluated several recent emerging anticoagulant drugs for use in patients with AF or ACS. The advantages of many new agents include predictable pharmaco-dynamic response and pharmacokinetic parameters, allowing for fixed oral dosing with no need for laboratory monitoring. For patients with AF, dabigatran is already approved for the prevention of stroke and systemic embolism, rivaroxaban appears to be an effective alternative to warfarin in high-risk patients, and apixaban may also be an effective alternative to aspirin in patients unable to take warfarin. Otamixaban shows promise as an intravenous alternative for patients with ACS in the acute care setting. Likewise, rivaroxaban, dabigatran, and darexaban with or without dual antiplatelet therapy may be beneficial for secondary prevention of ischemic events in patients with ACS.
血栓形成是许多心血管疾病的根本原因，动脉循环中的血栓形成可导致不稳定型心绞痛、心肌梗死或缺血性卒中。抗血栓治疗广泛应用，已被证实可预防心房颤动（AF）患者的缺血性卒中和血栓栓塞事件，或预防急性冠脉综合征（ACS）患者进一步发生缺血性并发症。传统抗凝剂（包括未分级肝素、低分子肝素和华法林）和抗血小板药物（包括阿司匹林、氯吡格雷和普拉格雷）通常用于这些适应证。它们的应用受限包括药代动力学和药效动力学特征的可变性、不能抑制纤维蛋白结合的凝血酶、肝素诱导的血小板减少症风险、作用起效延迟、众多药物相互作用、需要大量实验室监测和剂量滴定、低反应性或耐药性、过敏反应、不良反应和出血。为克服传统药物的一些局限性，新的抗血栓形成药物的开发更具针对性，高度选择性地针对特定的凝血因子，阻断凝血酶的合成。临床医生必须了解新的抗凝剂，以帮助为患者选择合适的治疗方法。我们描述了评价几种最近出现的新型抗凝药物在 AF 或 ACS 患者中应用的最相关的 II 期和 III 期临床试验。许多新型药物的优势包括可预测的药代动力学和药效动力学参数，允许固定的口服剂量，无需实验室监测。对于 AF 患者，达比加群已获准用于预防卒中和全身性栓塞，利伐沙班似乎是高危患者华法林的有效替代药物，阿哌沙班也可能是不能服用华法林的患者替代阿司匹林的有效药物。在急性治疗环境中，奥塔米昔单抗有望成为 ACS 患者的静脉替代药物。同样，利伐沙班、达比加群和达雷昔单抗联合或不联合双联抗血小板治疗可能对 ACS 患者的缺血性事件二级预防有益。
