Konieczny Kaja M, Dorian Paul
Division of Cardiology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
J Innov Card Rhythm Manag. 2019 Mar 15;10(3):3552-3559. doi: 10.19102/icrm.2019.100304. eCollection 2019 Mar.
Until the last decade, vitamin K antagonists (VKAs) were the only agents available for oral anticoagulation. Although effective and accessible, their use was complicated by a narrow therapeutic window, the need for regular monitoring of the international normalized ratio, and an associated susceptibility to interactions with both food and numerous medications. Furthermore, the onset of action was delayed, often requiring bridging with intravenous agents. In more recent years, we have enjoyed the development of nonvitamin-K-dependent, direct oral anticoagulants (DOACs), which either directly inhibit the activity of factor IIa (eg, dabigatran) or factor Xa (eg, rivaroxaban, apixaban, edoxaban). These medications boast a more rapid onset of action, predictable pharmacokinetics, wider therapeutic window, and equal or superior safety profiles. Although these medications appear to have fewer drug-drug interactions than VKAs, their interactions remain of clinical importance, particularly in one of the largest populations requiring anticoagulation: patients with atrial fibrillation. These patients are rarely on single medications, with the majority of them requiring some form of rate or rhythm control due to their arrhythmia. Unfortunately, data on interactions between DOACs and antiarrhythmic medications, despite their common coadministration, remain limited. Here, we summarize the interactions between antiarrhythmics and VKAs and review existing knowledge regarding their interactions with DOACs.
直到过去十年,维生素K拮抗剂(VKAs)一直是唯一可用于口服抗凝的药物。尽管它们有效且容易获得,但由于治疗窗狭窄、需要定期监测国际标准化比值以及与食物和多种药物相互作用的易感性,其使用变得复杂。此外,起效延迟,通常需要与静脉用药进行桥接。近年来,我们迎来了非维生素K依赖的直接口服抗凝剂(DOACs)的发展,这些药物要么直接抑制凝血因子IIa(如达比加群)的活性,要么抑制凝血因子Xa(如利伐沙班、阿哌沙班、依度沙班)的活性。这些药物起效更快、药代动力学可预测、治疗窗更宽,安全性相当或更优。尽管这些药物与VKAs相比似乎药物相互作用较少,但它们的相互作用在临床上仍然很重要,尤其是在需要抗凝的最大人群之一:房颤患者中。这些患者很少只服用单一药物,由于心律失常,大多数患者需要某种形式的心率或节律控制。不幸的是,尽管DOACs与抗心律失常药物经常联合使用,但关于它们之间相互作用的数据仍然有限。在此,我们总结抗心律失常药物与VKAs之间的相互作用,并回顾关于它们与DOACs相互作用的现有知识。