Kino Tabito, Nogami Akihiko, Soejima Kyoko, Uno Kikuya, Kumagai Koichiro, Kurita Takashi, Fukuzawa Masayuki, Takita Atsushi, Ishizu Tomoko, Aonuma Kazutaka
Department of Cardiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
Department of Cardiology, Kyorin University School of Medicine, Tokyo, Japan.
J Cardiovasc Electrophysiol. 2025 Mar;36(3):564-575. doi: 10.1111/jce.16560. Epub 2025 Jan 7.
Off-label under- and overdosing of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) is not uncommon in real-world practice.
This study aimed to identify efficacy and safety of off-label DOACs dose after AF ablation.
The RYOUMA registry was a prospective multicenter study of Japanese patients who underwent AF ablation between 2017 and 2018. DOAC prescriptions were categorized into on-label standard dose, on-label reduced dose, off-label underdose, and off-label overdose.
The proportion of off-label doses among patients after AF ablation varied depending on the type of DOAC, ranging from 13.5% to 34.9%. Of 2821 patients, 366 (13.0%) were prescribed an off-label underdose and exhibited significantly higher CHADS, CHADS-VASc, CHADS-VA, HELT-ES, and HAS-BLED scores, age, concomitant use of antiplatelets, and lower weight when compared to the on-label standard dose (n = 1809). While the incidence of ischemic stroke after 1 year of off-label underdose was notably low (0.28%), the rate of major bleeding was relatively high (1.7%). Off-label overdose was prescribed to 134 patients (4.8%), who showed a significantly higher incidence of major bleeding (3.0%) compared to on-label standard dose (0.91%; p = 0.02). The off-label overdose group did not have any particular background and its thromboembolic risk was, conversely, low. The most likely cause of off-label overdose was clinicians potentially overlooking dose criteria, including advanced age, low body weight, and low creatinine clearance.
In patients after AF ablation, off-label DOAC overdose was infrequent, but significantly associated with higher incidence of major bleeding during the remote period after AF ablation.
The study was registered as UMIN000026092 (University Hospital Medical Information Network-Clinical Trial Registry).
在现实临床实践中，心房颤动（AF）患者使用直接口服抗凝剂（DOACs）时出现超说明书用药的剂量不足和过量情况并不罕见。
本研究旨在确定房颤消融术后超说明书使用DOACs剂量的疗效和安全性。
RYOUMA注册研究是一项针对2017年至2018年间接受房颤消融术的日本患者的前瞻性多中心研究。DOAC处方被分为说明书规定的标准剂量、说明书规定的减量、超说明书用药的低剂量和超说明书用药的高剂量。
房颤消融术后患者中超说明书用药剂量的比例因DOAC类型而异，范围在13.5%至34.9%之间。在2821例患者中，366例（13.0%）被处方了超说明书用药的低剂量，与说明书规定的标准剂量组（n = 1809）相比，这些患者的CHADS、CHADS-VASc、CHADS-VA、HELT-ES和HAS-BLED评分、年龄、抗血小板药物的联合使用情况显著更高，而体重更低。虽然超说明书用药低剂量组在1年后缺血性卒中的发生率极低（0.28%），但大出血发生率相对较高（1.7%）。134例患者（4.8%）被处方了超说明书用药的高剂量，与说明书规定的标准剂量组（0.91%；p = 0.02）相比，这些患者大出血的发生率显著更高（3.0%）。超说明书用药高剂量组没有任何特殊背景，相反，其血栓栓塞风险较低。超说明书用药高剂量最可能的原因是临床医生可能忽略了剂量标准，包括高龄、低体重和低肌酐清除率。
在房颤消融术后患者中，超说明书使用DOACs高剂量的情况并不常见，但与房颤消融术后远期大出血发生率较高显著相关。
该研究已注册为UMIN000026092（大学医院医学信息网络 - 临床试验注册中心）。
