Wung Ju-Chieh, Hsu Chia-Chen, Wang Chi-En, Dong Yaa-Hui, Lin Chia-Chieh, Wang Szu-Yu, Chang Shih-Lin, Chang Yuh-Lih
Department of Pharmacy Taipei Veterans General Hospital, Taipei, Taiwan.
Department of Pharmacy College of Pharmaceutical Sciences National Yang Ming Chiao Tung University, Taipei, Taiwan.
Adv Pharmacol Pharm Sci. 2024 Sep 25;2024:9694592. doi: 10.1155/2024/9694592. eCollection 2024.
Pharmacokinetic studies have shown that rifampin reduces the levels of oral anticoagulants during the initiation of coadministration, raising concerns about an increased thrombotic risk, but there are limited comparative clinical outcomes between rifampin and warfarin compared with direct oral anticoagulants (DOACs). This study aimed to evaluate the effectiveness and safety of concurrent use of rifampin and warfarin versus DOACs, with assessments of outcome-associated factors and oral anticoagulant (OAC) management quality.
A total of 142 patients given rifampin plus warfarin ( = 56) or DOACs ( = 86) for over 7 days were included, and their clinical data and outcomes were compared.
The median Charlson Comorbidity Index and HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly, drugs/alcohol concomitantly) score of the two groups were 2 and 3, respectively. The incidence rate of composite ischemic or thromboembolic events was 2.16 and 1.44 per 10,000 patient-days in the warfarin and DOAC groups, respectively, with an adjusted hazard ratio (HR) of 0.41 (95% confidence interval [CI] 0.02-7.34). The incidence rate of composite major bleeding or clinically relevant nonmajor bleeding events was 1.58 and 1.52 per 10,000 patient-days in the warfarin and DOAC groups, respectively, with an adjusted HR of 1.12 (95% CI 0.32-4.45). The risk of composite bleeding events increased with a higher HAS-BLED score (HR: 1.62, 95% CI: 1.02-2.63). Moreover, 34.3% of warfarin users maintained a percent time in therapeutic range of above 50%. Furthermore, 77.9% of DOAC users received appropriate dosing.
No significant differences were observed in terms of the incidence of thrombotic or bleeding events between the two groups during coadministration. In addition, a higher HAS-BLED score was associated with a greater risk of bleeding events regardless of the class of OACs used. Finally, close monitoring of bleeding events should be considered.
药代动力学研究表明，在联合用药开始时，利福平会降低口服抗凝剂的水平，这引发了人们对血栓形成风险增加的担忧，但与直接口服抗凝剂（DOACs）相比，利福平和华法林之间的比较临床结果有限。本研究旨在评估利福平和华法林与DOACs联合使用的有效性和安全性，并评估与结果相关的因素和口服抗凝剂（OAC）管理质量。
共纳入142例接受利福平加华法林（n = 56）或DOACs（n = 86）治疗超过7天的患者，并比较他们的临床数据和结果。
两组的Charlson合并症指数中位数和HAS-BLED（高血压、肾/肝功能异常、中风、出血史或易感性、不稳定的国际标准化比值、老年人、同时使用药物/酒精）评分分别为2和3。华法林组和DOAC组复合缺血或血栓栓塞事件的发生率分别为每10000患者日2.16和1.44，调整后的风险比（HR）为0.41（95%置信区间[CI]0.02 - 7.34）。华法林组和DOAC组复合大出血或临床相关非大出血事件的发生率分别为每10000患者日1.58和1.52，调整后的HR为1.12（95%CI 0.32 - 4.45）。复合出血事件的风险随着HAS-BLED评分的升高而增加（HR：1.62，95%CI：1.02 - 2.63）。此外，34.3%的华法林使用者治疗范围内的时间百分比维持在50%以上。此外，77.9%的DOAC使用者接受了适当的剂量。
联合用药期间，两组在血栓形成或出血事件的发生率方面未观察到显著差异。此外，无论使用何种类型的OAC，较高的HAS-BLED评分与出血事件的风险增加相关。最后，应考虑密切监测出血事件。
