Faculty of Medicine, University of Belgrade, Serbia Cardiology Clinic, Clinical Center of Serbia, Serbia.
Adv Ther. 2012 Jun;29(6):491-507. doi: 10.1007/s12325-012-0026-8. Epub 2012 Jun 7.
Stroke prevention in atrial fibrillation (AF) has been challenging over decades, mostly due to a number of difficulties associated with oral vitamin K antagonists (VKAs), which have been the most effective stroke prevention treatment for a long time. The oral direct thrombin inhibitors (e.g., dabigatran) and oral direct inhibitors of factor Xa (e.g., rivaroxaban, apixaban) have emerged recently as an alternative to VKAs for stroke prevention in AF. These drugs act rapidly, and have a predictable and stable dose-related anticoagulant effect with a few clinically relevant drug-drug interactions. The novel oral anticoagulants are used in fixed doses with no need for regular laboratory monitoring of anticoagulation intensity. However, each of these drugs has distinct pharmacological properties that could influence optimal use in clinical practice. The following phase 3 randomized trials with novel oral anticoagulants versus warfarin for stroke prevention in AF have been completed: the Randomized Evaluation of Long-term Anticoagulant therapy (RE-LY) trial with dabigatran, the Rivaroxaban Once daily oral direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial with rivaroxaban, and the Apixaban for Reduction of Stroke and Other Thromboembolism Events in Atrial Fibrillation (ARISTOTLE) trial with apixaban. Moreover, the Apixaban Versus Acetylsalicylic Acid to prevent Strokes (AVERROES) trial included patients with AF who have failed or were unsuitable for warfarin, and compared apixaban versus aspirin for stroke prevention in AF. Overall, apixaban has two large trials for stroke prevention in AF showing benefits not only over warfarin, but also over aspirin among those patients who have failed or refused warfarin. In the ARISTOTLE trial, apixaban was superior to warfarin in the reduction of stroke or systemic embolism, major bleeding, intracranial hemorrhage, and all-cause mortality, with a similar reduction in the rate of ischemic stroke and better tolerability. When compared with aspirin in the AVERROES trial, apixaban was associated with more effective reduction of stroke, a similar risk of major bleeding, and better tolerability. In this review article, the authors summarize the current knowledge on novel oral anticoagulants and discuss the clinical aspects of their use for stroke prevention in AF, with particular emphasis on apixaban.
心房颤动（AF）的卒中预防几十年来一直是一个挑战，主要是因为口服维生素 K 拮抗剂（VKAs）存在许多困难，VKAs 长期以来一直是最有效的卒中预防治疗方法。口服直接凝血酶抑制剂（如达比加群）和口服 Xa 因子直接抑制剂（如利伐沙班、阿哌沙班）最近已成为 AF 卒中预防替代 VKAs 的方法。这些药物起效迅速，具有可预测和稳定的剂量相关抗凝作用，且与少数临床相关的药物相互作用。新型口服抗凝剂以固定剂量使用，无需常规监测抗凝强度的实验室监测。然而，每种药物都有其独特的药理学特性，这可能会影响其在临床实践中的最佳应用。以下是已完成的使用新型口服抗凝剂与华法林进行 AF 卒中预防的 3 期随机试验：达比加群的随机评价长期抗凝治疗（RE-LY）试验、利伐沙班的每日一次口服直接 Xa 因子抑制与维生素 K 拮抗剂预防 AF 卒中及栓塞试验（ROCKET-AF）试验和阿哌沙班预防 AF 卒中及其他血栓栓塞事件（ARISTOTLE）试验。此外，阿哌沙班用于预防 AF 患者卒中和其他血栓栓塞事件（AVERROES）试验包括 AF 患者，这些患者对华法林不耐受或无效，该试验比较了阿哌沙班与阿司匹林在 AF 中的卒中预防作用。总体而言，阿哌沙班有两项大型 AF 卒中预防试验，不仅显示优于华法林，而且对于那些对华法林不耐受或拒绝使用华法林的患者，也优于阿司匹林。在 ARISTOTLE 试验中，与华法林相比，阿哌沙班在降低卒中或全身性栓塞、大出血、颅内出血和全因死亡率方面更优，且缺血性卒中和更好的耐受性方面的发生率相似。在 AVERROES 试验中，与阿司匹林相比，阿哌沙班在降低卒中方面更有效，大出血风险相似，且耐受性更好。在这篇综述文章中，作者总结了新型口服抗凝剂的现有知识，并讨论了其在 AF 卒中预防中的临床应用，特别强调了阿哌沙班。
