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Stroke Prevention in Atrial Fibrillation: Understanding the New Oral Anticoagulants Dabigatran, Rivaroxaban, and Apixaban

机译:心房颤动的卒中预防:了解新型口服抗凝药达比加群,利伐沙班和阿哌沙班

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Unlike vitamin K antagonists (VKAs), the new oral anticoagulants (NOACs)—direct thrombin inhibitor, dabigatran, and direct activated factor X inhibitors, rivaroxaban, and apixaban—do not require routine INR monitoring. Compared to VKAs, they possess relatively rapid onset of action and short halflives, but vary in relative degrees of renal excretion as well as interaction with p-glycoprotein membrane transporters and liver cytochrome P450 metabolic enzymes. Recent completed phase III trials comparing NOACs with VKAs for stroke prevention in atrial fibrillation (AF)—the RE-LY, ROCKET AF, and ARISTOTLE trials—demonstrated at least noninferior efficacy, largely driven by significant reductions in haemorrhagic stroke. Major and nonmajor clinically relevant bleeding rates were acceptable compared to VKAs. Of note, the NOACs caused significantly less intracranial haemorrhagic events compared to VKAs, the mechanisms of which are not completely clear. With convenient fixed-dose administration, the NOACs facilitate anticoagulant management in AF in the community, which has hitherto been grossly underutilised. Guidelines should evolve towards simplicity in anticipation of greater use of NOACs among primary care physicians. At the same time, the need for caution with their use in patients with severely impaired renal function should be emphasised.
机译:与维生素K拮抗剂(VKA)不同,新型口服抗凝剂(NOAC)-直接凝血酶抑制剂,达比加群和直接活化的X因子抑制剂利伐沙班和阿哌沙班-不需要常规INR监测。与VKA相比,它们起效相对较快,半衰期较短,但肾脏排泄的相对程度以及与p糖蛋白膜转运蛋白和肝细胞色素P450代谢酶的相互作用不同。最近完成的III期试验比较了NOAC和VKA在房颤(AF)预防卒中中的作用(RE-LY,ROCKET AF和ARISTOTLE试验)至少显示了非劣效,这在很大程度上是由出血性卒中的明显减少所致。与VKA相比,主要和非主要临床相关出血率是可以接受的。值得注意的是,与VKA相比,NOAC引起的颅内出血事件明显少得多,其机制尚不完全清楚。通过方便的固定剂量给药,NOAC促进了社区房颤的抗凝剂管理,而迄今为止,这种抗凝剂的使用率仍然很低。指导原则应朝着简化的方向发展,以期在初级保健医生中更多地使用NOAC。同时,应强调在肾功能严重受损的患者中谨慎使用它们的必要性。

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