Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Drug Des Devel Ther. 2021 May 6;15:1931-1943. doi: 10.2147/DDDT.S303219. eCollection 2021.
Considering that the current fixed dose of direct oral anticoagulants (DOACs) might have insufficient anticoagulation effect for overweight patients, the aim of this study was to compare the effectiveness and safety of anticoagulation between dabigatran and rivaroxaban in different body mass index (BMI) population.
We conducted a retrospective cohort study of 2402 DOAC anticoagulated patients with atrial fibrillation who underwent catheter ablation (1290 dabigatran, 53.7% and 1112 rivaroxaban, 46.3%) between January 2017 and December 2018. Patients were distributed based on the BMI into nonobese (1362, BMI <25 kg/m), preobese (521, BMI 25.0-29.9 kg/m), class I obese (344, BMI 30.0-34.9 kg/m) and class II+ obese (175, BMI ≥35.0 kg/m). We collected information regarding clinical features, laboratory data, bleeding complications and systemic embolic events from the electrical medical records system during 12 months.
The incidence of systemic embolism and stroke complications was higher in the class II+ obese group (=0.001 and =0.003). The incidence of bleeding complications and the levels of anticoagulation parameters under the bleeding threshold were similar among the four groups (>0.05). Cumulative Kaplan-Meier analysis illustrated that rivaroxaban-treated patients who belonged to higher BMI subgroups were more likely to experience shorter time to thrombosis (TTT) (12-month TTT rates of 0.5% for nonobese vs 1.7% for class I obese patients, HR=3.716, =0.005; 12-month TTT rates of 0.5%, for nonobese vs 4.0% for class II+ obese patients, HR=6.843, =0.001). However, no statistical significant difference in terms of the time to bleeding complications and the time to cumulative events among the four groups was observed. By multivariate analysis, a higher BMI value (BMI ≥25 kg/m) (=0.019; OR=2.094, 95%CI: 1.129-3.883) was an independent predictor for thrombosis in patients treated with dabigatran or rivaroxaban. Positive linear relationship was observed between BMI levels and occurrence rate of thrombosis and bleeding in under anticoagulation patients with NVAF (R=0.451 and R=0.383, respectively).
The fixed dose of 15 mg rivaroxaban might carry a risk of under exposure, which would lead to an increase of thromboembolic complications in patients with high BMI. Therefore, rivaroxaban dose increase was suggested for obese patients. Use of DOACs appears to have considerable safety in obese patients.
考虑到目前直接口服抗凝剂（DOACs）的固定剂量可能对超重患者的抗凝效果不足，本研究旨在比较达比加群和利伐沙班在不同体重指数（BMI）人群中的抗凝效果和安全性。
我们对 2017 年 1 月至 2018 年 12 月期间接受导管消融治疗的 2402 例房颤 DOAC 抗凝患者进行了回顾性队列研究（达比加群 1290 例，53.7%；利伐沙班 1112 例，46.3%）。根据 BMI 将患者分为非肥胖组（1362 例，BMI<25kg/m2）、超重组（521 例，BMI 25.0-29.9kg/m2）、I 级肥胖组（344 例，BMI 30.0-34.9kg/m2）和 II+级肥胖组（175 例，BMI≥35.0kg/m2）。我们从电子病历系统中收集了 12 个月内的临床特征、实验室数据、出血并发症和系统性栓塞事件信息。
II+级肥胖组的系统性栓塞和中风并发症发生率较高（=0.001 和=0.003）。在四个组中，出血并发症的发生率和低于出血阈值的抗凝参数水平相似（>0.05）。累积 Kaplan-Meier 分析表明，属于较高 BMI 亚组的利伐沙班组患者更有可能经历较短的血栓形成时间（TTT）（非肥胖组的 12 个月 TTT 率为 0.5%，I 级肥胖组为 1.7%，HR=3.716，=0.005；非肥胖组的 12 个月 TTT 率为 0.5%，II+级肥胖组为 4.0%，HR=6.843，=0.001）。然而，在四个组之间，出血并发症时间和累积事件时间方面没有观察到统计学上的显著差异。多变量分析显示，较高的 BMI 值（BMI≥25kg/m2）（=0.019；OR=2.094，95%CI：1.129-3.883）是达比加群或利伐沙班治疗患者发生血栓的独立预测因素。在未抗凝的 NVAF 患者中，BMI 水平与血栓形成和出血发生率呈正相关（R=0.451 和 R=0.383）。
固定剂量的 15mg 利伐沙班可能存在剂量不足的风险，这会导致 BMI 较高的患者血栓栓塞并发症增加。因此，建议肥胖患者增加利伐沙班的剂量。DOAC 的使用在肥胖患者中似乎具有相当的安全性。
