Department of Medicine, McMaster University, Hamilton, Ontario, Canada2Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada3Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada4Hamilton Health Sciences, Hamilton, Ontario, Canada.
Department of Radiology, King's College Hospital, London, England.
JAMA Cardiol. 2017 May 1;2(5):566-574. doi: 10.1001/jamacardio.2017.0364.
The non-vitamin K antagonist oral anticoagulants (NOACs) apixaban, dabigatran, edoxaban, and rivaroxaban are administered in fixed doses without anticoagulant monitoring. Randomized trials show that unmonitored NOAC therapy is at least as effective as and safer than dose-adjusted warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. Subgroup analyses indicate that plasma drug levels or anticoagulant activity of the NOACs predict stroke and bleeding. This review examines the historical basis for anticoagulant monitoring, discusses methods to measure and interpret drug levels, and critically assesses the role of routine laboratory monitoring in the management of NOAC therapy.
The predictable anticoagulant response of NOACs has provided the pharmacological basis for their administration in fixed doses without routine coagulation monitoring. Although it is possible to accurately measure NOAC drug levels, within-patient variability complicates interpretation of these results. Furthermore, patient characteristics, such as age and renal function, confound the association between NOAC drug levels and clinical outcomes. Information is lacking on the optimal drug level in particular patient groups (eg, elderly, the renally impaired, and those with high bleeding risk), the appropriate dose adjustment to achieve expected levels, and whether routine laboratory monitoring and dose adjustment will improve clinical outcomes. A benefit of a management strategy that incorporates routine therapeutic drug monitoring and dose adjustment over current standard-of-care metrics without such monitoring remains unproven.
Robust evidence from patients with atrial fibrillation randomized to NOACs or warfarin demonstrates that unmonitored NOAC therapy is at least as effective and safe as monitored warfarin, with lower rates of intracranial hemorrhage and reduced mortality. Further research is required to determine whether routine laboratory monitoring might provide a net benefit for patients. Until such data are available, clinicians should continue to prescribe NOACs in fixed doses without routine monitoring.
非维生素 K 拮抗剂口服抗凝剂（NOACs）阿哌沙班、达比加群、依度沙班和利伐沙班以固定剂量给药，无需抗凝监测。随机试验表明，与剂量调整华法林相比，未经监测的 NOAC 治疗在预防非瓣膜性心房颤动患者中风方面至少同样有效且更安全。亚组分析表明，NOAC 的血浆药物水平或抗凝活性可预测中风和出血。本综述检查了抗凝监测的历史基础，讨论了测量和解释药物水平的方法，并批判性地评估了常规实验室监测在 NOAC 治疗管理中的作用。
NOAC 的可预测抗凝反应为其无需常规凝血监测即可固定剂量给药提供了药理学基础。虽然可以准确测量 NOAC 药物水平，但个体内的变异性使这些结果的解释变得复杂。此外，患者特征，如年龄和肾功能，使 NOAC 药物水平与临床结果之间的关联复杂化。缺乏关于特定患者群体（例如，老年人、肾功能不全者和高出血风险者）的最佳药物水平、实现预期水平的适当剂量调整以及常规实验室监测和剂量调整是否会改善临床结果的信息。一种将常规治疗药物监测和剂量调整纳入管理策略的益处，与没有这种监测的当前标准护理指标相比，是否能改善临床结果仍有待证明。
来自随机分配至 NOAC 或华法林的心房颤动患者的强有力证据表明，未经监测的 NOAC 治疗至少与监测的华法林一样有效且安全，颅内出血发生率较低，死亡率降低。需要进一步研究以确定常规实验室监测是否可能为患者带来净收益。在获得此类数据之前，临床医生应继续以固定剂量开处方 NOAC，而无需常规监测。
