Department of Cardiology, Osaka Police Hospital, Osaka, Japan.
Department of Cardiology, Osaka Police Hospital, Osaka, Japan; Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Am J Cardiol. 2021 Jan 15;139:50-56. doi: 10.1016/j.amjcard.2020.09.053. Epub 2020 Oct 13.
The present study aimed to assess the associations between dosing of DOACs and outcomes in patients with non-valvular atrial fibrillation (NVAF). Direct oral anticoagulants (DOACs) require dose adjustment according to patient or clinical factors for patients with NVAF. We conducted a single-center prospective registry of NVAF patients with DOACs: DIRECT registry (UMIN000033283). In the present analysis, we categorized the patients (n = 2,216) into 5 groups: appropriate standard-dose (n = 907, 40.9%), appropriate low-dose (n = 833, 37.6%), overdose (n = 117, 5.3%), underdose (n = 338, 15.3%), and contraindication (n = 21, 0.9%). The efficacy endpoints were major adverse cardiovascular event (MACE: a composite of all-cause death, myocardial infarction, and stroke/systemic embolism) and its individual components. The safety end points were adverse bleeding events including clinically significant bleeding, major bleeding, and gastro-intestinal bleeding. All NVAF patients treated with DOACs in our institution from 2011 to 2017 were enrolled (71.6 ± 10.8 years, 36.4% female, follow-up duration: 407.2 ± 388.3 days). Appropriate low-dose group were older, more likely female, had a higher CHADS and ORBIT scores than the other groups. MACE (7.4%) and clinically significant bleeding (26.2%) occurred most frequently in the appropriate low-dose group. However, after adjustment for various confounders, appropriate dose reduction of DOAC showed 35.4% risk reduction of clinically significant bleeding (adjusted hazard ratio 0.646, 95% CI [0.469 to 0.890], p = 0.007) with no impairment of efficacy end points. In the real-world Asian clinical practice, four fifths of the NVAF patients received appropriate dose of DOACs. Appropriate dose reduction was associated with decrease in clinically significant bleeding and no significant impairment in efficacy end points.
本研究旨在评估非瓣膜性心房颤动（NVAF）患者使用直接口服抗凝剂（DOAC）的剂量与结局之间的关系。对于 NVAF 患者，DOAC 需要根据患者或临床因素进行剂量调整。我们进行了一项关于 NVAF 患者使用 DOAC 的单中心前瞻性登记研究：DIRECT 登记研究（UMIN000033283）。在本分析中，我们将患者（n=2216）分为 5 组：适当标准剂量组（n=907，40.9%）、适当低剂量组（n=833，37.6%）、超剂量组（n=117，5.3%）、低剂量组（n=338，15.3%）和禁忌证组（n=21，0.9%）。疗效终点为主要不良心血管事件（MACE：全因死亡、心肌梗死和卒中/全身性栓塞的复合终点）及其各组成部分。安全性终点为不良出血事件，包括临床显著出血、大出血和胃肠道出血。我们机构 2011 年至 2017 年期间所有接受 DOAC 治疗的 NVAF 患者均纳入研究（71.6±10.8 岁，36.4%为女性，随访时间：407.2±388.3 天）。适当低剂量组年龄较大，女性比例较高，CHA2DS2-VASc 和 ORBIT 评分均高于其他组。MACE（7.4%）和临床显著出血（26.2%）在适当低剂量组中最常见。然而，在调整了各种混杂因素后，DOAC 的适当剂量减少与临床显著出血风险降低 35.4%相关（调整后的危险比为 0.646，95%CI[0.469 至 0.890]，p=0.007），且对疗效终点无影响。在亚洲真实世界临床实践中，五分之四的 NVAF 患者接受了 DOAC 的适当剂量。适当剂量减少与临床显著出血减少相关，且对疗效终点无显著影响。
