Off-label underdosing of edoxaban antithrombotic therapy for patients with atrial fibrillation and stable coronary artery disease: findings from the EPIC-CAD trial.
Min Soo Cho, Do-Yoon Kang, Jung-Bok Lee, Yong-Seog Oh, Chang Hoon Lee, Eue-Keun Choi, Ji Hyun Lee, Chang Hee Kwon, Gyung-Min Park, Hyung Oh Choi, Kyoung-Ha Park, Kyoung-Min Park, Jongmin Hwang, Ki-Dong Yoo, Young Rak Cho, Ji-Hyun Kim, Ki Won Hwang, Eun Sun Jin, Osung Kwon, Ki-Hun Kim, Duk-Woo Park, Gi-Byoung Nam
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引用次数: 0
Abstract
Objective: The impact of off-label underdosing of direct oral anticoagulants (DOACs) on clinical outcomes in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) remains unclear.
Methods: The EPIC-CAD trial (Edoxaban vs Edoxaban with antiPlatelet agent In patients with atrial fibrillation and Chronic stable Coronary Artery Disease) randomised patients with AF and stable CAD to receive either edoxaban monotherapy or dual antithrombotic therapy (edoxaban plus single antiplatelet agent). Off-label underdosing was defined as low-dose edoxaban (30 mg once daily) without standard criteria for dose reduction. The primary outcome was a composite of death, myocardial infarction, stroke, systemic embolism, unplanned revascularisation and major or clinically relevant non-major bleeding at 12 months.
Results: Among the 1040 randomised patients, 694 patients (66.7%) without dose-reduction criteria were included; of whom, 121 patients (17.4%) received edoxaban underdosing. At 12 months, the incidence of primary outcome was similar between standard-dose and under-dose edoxaban groups (10.5% vs 9.2%, adjusted HR 0.77, 95% CI 0.39 to 1.54). There was no significant difference in major ischaemic events (1.4% vs 1.7%, HR 1.14, 95% CI 0.22 to 5.91) and major or clinically relevant non-major bleeding (9.0% vs 8.4%, HR 0.87, 95% CI 0.42 to 1.78). Regardless of edoxaban underdosing, edoxaban monotherapy was associated with lower risk of primary net-clinical outcomes and bleeding compared with dual antithrombotic therapy.
Conclusions: In patients with AF and stable CAD, there was no significant difference in the rate of primary outcome between off-label underdose and standard-dose edoxaban. The benefit of edoxaban monotherapy over dual antithrombotic therapy was consistent regardless of edoxaban underdosing. However, given the analyses were underpowered and the CI was wide, the results cannot be considered clinically directive.
目的：直接口服抗凝剂（DOACs）超说明书剂量不足对房颤（AF）合并稳定型冠状动脉疾病（CAD）患者临床结局的影响尚不清楚。方法：EPIC-CAD试验（edo沙班vs edo沙班联合抗血小板药物治疗心房颤动和慢性稳定型冠状动脉疾病患者）将房颤和稳定型冠心病患者随机分组，接受edo沙班单药治疗或双重抗血栓治疗（edo沙班联合单一抗血小板药物）。超说明书剂量不足被定义为低剂量的依多沙班（30mg每日一次），没有标准的剂量减少标准。主要结局是12个月时死亡、心肌梗死、中风、全身性栓塞、计划外血运重建术和重大或临床相关的非重大出血的综合结果。结果：在1040例随机分组患者中，纳入了694例（66.7%）无减量标准患者；其中121例（17.4%）患者接受了edo沙班剂量不足。在12个月时，标准剂量组和低剂量组的主要结局发生率相似（10.5% vs 9.2%，调整后HR 0.77, 95% CI 0.39 ~ 1.54）。主要缺血事件（1.4% vs 1.7%, HR 1.14, 95% CI 0.22 ~ 5.91）和主要或临床相关的非主要出血（9.0% vs 8.4%, HR 0.87, 95% CI 0.42 ~ 1.78）无显著差异。不管伊多沙班是否剂量不足，与双重抗血栓治疗相比，伊多沙班单药治疗的主要净临床结果和出血风险较低。结论：在房颤合并稳定型CAD患者中，超说明书剂量不足和标准剂量依多沙班的主要转归率无显著差异。单药edo沙班治疗优于双药抗血栓治疗的益处是一致的，无论edo沙班剂量是否不足。然而，考虑到分析能力不足，CI范围很广，结果不能被认为具有临床指导意义。试用注册号：URL: https://www.Clinicaltrials: gov；唯一标识符：NCT03718559。
期刊介绍：
Heart is an international peer reviewed journal that keeps cardiologists up to date with important research advances in cardiovascular disease. New scientific developments are highlighted in editorials and put in context with concise review articles. There is one free Editor’s Choice article in each issue, with open access options available to authors for all articles. Education in Heart articles provide a comprehensive, continuously updated, cardiology curriculum.
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