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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。

Stroke prevention in atrial fibrillation: understanding the new oral anticoagulants dabigatran, rivaroxaban, and apixaban.

作者信息

Ru San Tan, Chan Mark Yan Yee, Wee Siong Teo, Kok Foo Tang, Kheng Siang Ng, Lee Sze Huar, Chi Keong Ching

机构信息

Department of Cardiology, National Heart Centre Singapore, 17 Third Hospital Avenue, Singapore 168752 ; Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857.

出版信息

Thrombosis. 2012;2012:108983. doi: 10.1155/2012/108983. Epub 2012 Sep 10.

Abstract

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.

摘要

与维生素K拮抗剂(VKA)不同,新型口服抗凝药(NOAC)——直接凝血酶抑制剂达比加群以及直接活化因子X抑制剂利伐沙班和阿哌沙班——不需要常规监测国际标准化比值(INR)。与VKA相比,它们起效相对较快,半衰期较短,但在肾脏排泄的相对程度以及与P-糖蛋白膜转运体和肝细胞色素P450代谢酶的相互作用方面存在差异。最近完成的比较NOAC与VKA用于心房颤动(AF)患者预防卒中的III期试验——RE-LY、ROCKET AF和ARISTOTLE试验——显示至少具有非劣效性疗效,这在很大程度上是由于出血性卒中显著减少所致。与VKA相比,主要和非主要的临床相关出血率是可接受的。值得注意的是,与VKA相比,NOAC引起的颅内出血事件明显更少,其机制尚不完全清楚。由于采用方便的固定剂量给药,NOAC便于在社区中对AF患者进行抗凝管理,而此前这方面的应用严重不足。随着初级保健医生对NOAC的使用增加,指南应朝着简化的方向发展。与此同时,应强调在严重肾功能受损患者中谨慎使用NOAC的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1eed/3444866/0e5ce14b7da7/THROMB2012-108983.001.jpg

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