Department of Pharmacy, Kobe City Medical Center General Hospital.
Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital.
Biol Pharm Bull. 2020 Mar 1;43(3):458-462. doi: 10.1248/bpb.b19-00799. Epub 2019 Dec 18.
Edoxaban is used to prevent and treat stroke or systemic embolism such as venous thromboembolism. Although bleeding is the most common complication of anticoagulants, only a few studies have addressed the safety of direct oral anticoagulants in East Asian patients. In this study, we investigated the risk factors for bleeding in Japanese patients receiving edoxaban. A retrospective review of the records of 198 patients who received 30 mg/d edoxaban in our hospital between April 2015 and March 2017 was performed. Subsequently, these patients were followed up to 1 year. Seven (3.5%) and 22 (11.1%) patients developed major bleeding and clinically relevant bleeding, respectively. In the univariate Cox regression analyses, low baseline hemoglobin levels (p = 0.002) and low baseline creatinine clearance (p = 0.020) were significantly associated with major bleeding. Multivariate Cox regression analysis revealed that a low baseline hemoglobin level was a significant risk factor for major bleeding and clinically relevant bleeding [hazard ratio 1.67 per 1 g/dL decrease (95% confidence interval 1.14-2.56, p = 0.008) and hazard ratio 1.31 per 1 g/dL decrease (95% confidence interval 1.06-1.62, p = 0.013), respectively]. Baseline hemoglobin level in quartiles also showed a quartile-dependent decrease in major bleeding and clinically relevant bleeding event. These results suggest that low baseline hemoglobin level is a significant risk factor for both major bleeding and clinically relevant bleeding in Japanese patients receiving edoxaban. Thus, these patients should be carefully monitored.
依度沙班用于预防和治疗卒中和全身性栓塞，如静脉血栓栓塞。尽管出血是抗凝剂最常见的并发症，但只有少数研究探讨了东亚患者使用直接口服抗凝剂的安全性。在这项研究中，我们调查了接受依度沙班治疗的日本患者出血的危险因素。对 2015 年 4 月至 2017 年 3 月期间在我院接受 30mg/d 依度沙班治疗的 198 例患者的病历进行了回顾性分析。随后对这些患者进行了为期 1 年的随访。7（3.5%）例和 22（11.1%）例患者分别发生了大出血和临床相关出血。单因素 Cox 回归分析显示，基线血红蛋白水平较低（p=0.002）和基线肌酐清除率较低（p=0.020）与大出血显著相关。多因素 Cox 回归分析显示，基线血红蛋白水平较低是大出血和临床相关出血的显著危险因素[血红蛋白每降低 1g/dL，风险比为 1.67（95%置信区间 1.14-2.56，p=0.008）和 1.31（95%置信区间 1.06-1.62，p=0.013）]。血红蛋白水平 quartiles 也显示大出血和临床相关出血事件呈 quartile 依赖性下降。这些结果表明，基线血红蛋白水平较低是日本接受依度沙班治疗的患者发生大出血和临床相关出血的显著危险因素。因此，应对这些患者进行密切监测。
