McMaster University, Hamilton, Ontario, Canada.
Stanford University, Palo Alto, CA.
Am Heart J. 2018 May;199:59-67. doi: 10.1016/j.ahj.2017.10.002. Epub 2017 Oct 10.
The novel direct oral anticoagulants (NOACs) represent a major advance in oral anticoagulant therapy and are replacing vitamin K antagonists as the preferred options for many indications. Given in fixed doses without routine laboratory monitoring, they have been shown to be at least as effective in reducing thromboembolic stroke as dose-adjusted warfarin in phase 3 randomized trials and less likely to cause hemorrhagic stroke. Pharmacokinetic and/or pharmacodynamic subanalyses of the major NOAC trials in patients with atrial fibrillation have established relationships between clinical characteristics, and drug levels and/or pharmacodynamic responses with both efficacy and safety. Based on these analyses, pharmaceutical manufacturers and regulatory authorities have provided contraindications and dosing recommendations based on clinical characteristics that are associated with drug levels and/or pharmacodynamic responses, stroke reduction, and bleeding risk to optimize the risk-benefit profile of the NOACs in the real world. The current fixed-dosing strategy of NOACs has triggered discussions about the potential value of laboratory monitoring and dose adjustment in customizing drug exposure to further improve the safety and efficacy of the NOACs in patients with atrial fibrillation. As there is neither high-quality evidence nor consensus about the potential role of laboratory monitoring and dose adjustment for the NOACs, a Cardiac Research Safety Consortium "Think Tank" meeting was held at the American College of Cardiology Heart House in December 2015 to discussions these issues. This manuscript reports on the deliberations and the conclusions reached at that meeting.
新型直接口服抗凝剂（NOACs）是口服抗凝治疗领域的重大进展，正在取代维生素 K 拮抗剂，成为许多适应证的首选药物。NOACs 无需常规实验室监测即可固定剂量给药，其在 3 期随机试验中在降低血栓栓塞性卒中和减少出血性卒中方面的疗效至少与剂量调整华法林相当。在房颤患者中进行的主要 NOAC 试验的药代动力学和/或药效动力学亚分析已确定了临床特征与药物浓度和/或药效动力学反应之间的关系，这些关系与疗效和安全性均相关。基于这些分析，制药商和监管机构根据与药物浓度和/或药效动力学反应、卒中减少和出血风险相关的临床特征，为 NOACs 提供了禁忌证和剂量建议，以优化 NOAC 在真实世界中的风险-效益比。目前，NOAC 的固定剂量策略引发了关于实验室监测和剂量调整在使药物暴露个体化以进一步提高房颤患者的安全性和疗效方面潜在价值的讨论。由于目前尚无关于实验室监测和剂量调整对 NOACs 潜在作用的高质量证据和共识，因此 2015 年 12 月在美国心脏病学会心脏大厦举行了心血管研究安全联盟“思维碰撞”会议，以讨论这些问题。本文报告了该会议的讨论情况和达成的结论。
