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[新型口服抗凝药与老年人房颤]

[Novel oral anticoagulants and atrial fibrillation in the elderly].

作者信息

Hanon Olivier

机构信息

Service de gérontologie, Hôpital Broca, Paris, France.

出版信息

Geriatr Psychol Neuropsychiatr Vieil. 2013 Dec;11(1 Suppl):34-40. doi: 10.1684/pnv.2013.0444.

Abstract

Atrial fibrillation treatment relies on anticoagulation therapy that reduces the risk of stroke. Vitamin K antagonists (VKA) were the only oral anticoagulant drugs for more than 50 years, but they are difficult to manage especially in the elderly. In France, VKA are the main cause of iatrogenic hospitalizations with about 17,000 hospitalizations per year and around 4,000 to 5,000 deaths per year. Pharmacologic properties of VKA, especially the narrow therapeutic margin explain the complexity of their management. Several studies have shown that patients treated with VKA were on average only 50% of the time with an INR in the therapeutic range. In other words, patients are, half of the time, either-under treated or over-treated. Within this framework, development of new oral anticoagulant drugs appeared necessary, in order to obtain drugs with larger therapeutic margin and a better risk/benefit profile than VKA. Three large randomized clinical trials including almost 50,000 patients with 20,000 subjects over 75 years old and 8,000 over 80 years old, show a better risk/benefit profile of the new oral anticoagulants (NOAC) than VKA, characterized by a 50% reduction of cerebral hemorrhages, 22% reduction of stroke and 12% reduction of total mortality. Meanwhile, their renal elimination and the lack of control of the biological efficacy need to be taken into account for their prescription. Renal failure (estimated glomerular filtration rate according to Cockcroft formula < 30 mL/min) contraindicates their use. Their half-life is shorter than that of VKA and the biological monitoring is not available, thus a good adherence to the treatment is important. Studies specifically conducted among geriatric older population with poly-pathologies and frail are therefore needed to evaluate tolerance of NOAC in real life conditions.

摘要

心房颤动的治疗依赖于降低中风风险的抗凝治疗。维生素K拮抗剂(VKA)在50多年的时间里一直是唯一的口服抗凝药物,但它们难以管理,尤其是在老年人中。在法国,VKA是医源性住院的主要原因,每年约有17000例住院病例,每年约有4000至5000人死亡。VKA的药理特性,尤其是其狭窄的治疗窗,解释了其管理的复杂性。多项研究表明,接受VKA治疗的患者平均只有50%的时间国际标准化比值(INR)处于治疗范围内。换句话说,患者有一半的时间要么治疗不足,要么治疗过度。在此背景下,开发新的口服抗凝药物显得很有必要,以便获得比VKA具有更宽治疗窗和更好风险/效益比的药物。三项大型随机临床试验纳入了近50000名患者,其中20000名受试者年龄在75岁以上,8000名受试者年龄在80岁以上,结果显示新型口服抗凝药(NOAC)的风险/效益比优于VKA,其特点是脑出血减少50%,中风减少22%,总死亡率减少12%。同时,在开具其处方时需要考虑到它们通过肾脏排泄以及缺乏生物疗效监测的情况。肾衰竭(根据Cockcroft公式估算的肾小球滤过率<30 mL/min)为使用它们的禁忌证。它们的半衰期比VKA短,且无法进行生物监测,因此良好的治疗依从性很重要。因此,需要专门针对患有多种疾病和身体虚弱的老年人群体进行研究,以评估NOAC在现实生活条件下的耐受性。

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