Department of Polyvalent Medicine, Valenciennes General Hospital, 114 avenue Desandrouin, 59300, Valenciennes, France.
Clinical Research Unit-Clinical Pharmacy, Valenciennes General Hospital, Valenciennes, France.
Drugs Aging. 2021 Oct;38(10):939-950. doi: 10.1007/s40266-021-00883-1. Epub 2021 Sep 6.
Direct oral anticoagulants (DOACs) are currently recommended as first-line or (after vitamin K antagonists) second-line therapy for preventing stroke and systemic embolism in patients with non-valvular atrial fibrillation. In patients aged 80 years and over, however, the fear of DOAC-associated bleeding and the complexity of DOAC dosing regimes may prompt physicians to prescribe inappropriate dose levels.
The objective of this study was to determine compliance with French and European guidelines of doses of three DOACs (apixaban, dabigatran and rivaroxaban) prescribed to patients aged over 80 years in an indication of non-valvular atrial fibrillation, and to identify factors associated with poor compliance.
We performed a retrospective single-centre study of patients aged over 80 years routinely treated with a DOAC (apixaban, dabigatran or rivaroxaban) for non-valvular atrial fibrillation at Valenciennes General Hospital (Valenciennes, France) between 1 January, 2016 and 31 December, 2017. We determined compliance with French and European guidelines of DOAC doses as a function of each patient's clinical and laboratory parameters, and thus classified the regime as being appropriately dosed, overdosed or underdosed.
A total of 703 patients (371 taking apixaban, 92 taking dabigatran and 240 taking rivaroxaban) were included in the study. We found that 274 patients (39%) had been prescribed an inappropriate DOAC regime, with underdosing in 241 cases (34%) and overdosing in 33 cases (5%). Underdosing mainly concerned the two most widely prescribed DOACs, i.e. apixaban (39% of all apixaban prescriptions were underdosed) and rivaroxaban (40%). Concomitant treatment with an antidepressant was associated with underdosing of rivaroxaban or apixaban (p = 0.0339). In contrast, initial management in a neurology department was associated with appropriate dosing (p = 0.000146) for both these DOACs.
Among patients with non-valvular atrial fibrillation aged 80 years and over, about 40% of DOAC prescriptions feature inappropriate dose levels. It might be possible to reduce inappropriate dosing by raising awareness among hospital-based and private-practice prescribers, providing prescription support tools for DOACs, and performing medication reconciliations and reviews at hospital and in private practice.
直接口服抗凝剂（DOACs）目前被推荐用于预防非瓣膜性心房颤动患者的中风和全身性栓塞，作为一线或（维生素 K 拮抗剂后）二线治疗。然而，对于 80 岁及以上的患者，由于担心 DOAC 相关出血以及 DOAC 剂量方案的复杂性，医生可能会开出不合适的剂量水平。
本研究的目的是确定法国和欧洲三项 DOAC （阿哌沙班、达比加群和利伐沙班）剂量指南在非瓣膜性心房颤动适应证中，对 80 岁以上患者的用药依从性，并确定与不依从相关的因素。
我们进行了一项回顾性单中心研究，研究对象为 2016 年 1 月 1 日至 2017 年 12 月 31 日期间，在法国瓦朗谢讷总医院（Valenciennes，法国）常规接受 DOAC（阿哌沙班、达比加群或利伐沙班）治疗的 80 岁以上非瓣膜性心房颤动患者。我们根据每位患者的临床和实验室参数确定 DOAC 剂量是否符合法国和欧洲指南，从而将治疗方案分为剂量适当、剂量过高或剂量过低。
共纳入 703 例患者（阿哌沙班 371 例，达比加群 92 例，利伐沙班 240 例）。我们发现 274 例（39%）患者处方的 DOAC 方案不适当，其中 241 例（34%）剂量过低，33 例（5%）剂量过高。剂量过低主要涉及两种应用最广泛的 DOAC，即阿哌沙班（所有阿哌沙班处方中有 39%剂量过低）和利伐沙班（40%）。同时使用抗抑郁药与利伐沙班或阿哌沙班的剂量过低有关（p=0.0339）。相比之下，神经内科初始治疗与这两种 DOAC 的适当剂量相关（p=0.000146）。
在 80 岁及以上非瓣膜性心房颤动患者中，约 40%的 DOAC 处方剂量水平不适当。通过提高医院和私人诊所开处方者的认识，提供 DOAC 处方支持工具，并在医院和私人诊所进行药物调整和审查，可能会减少不适当的剂量。
