Janssen Pharmaceuticals, Inc, 1125 Trenton Harbourton Rd, Titusville, NJ, 08560, USA.
Janssen Research & Development, LLC, Raritan, NJ, USA.
Am J Cardiovasc Drugs. 2023 May;23(3):247-255. doi: 10.1007/s40256-023-00579-4. Epub 2023 Apr 28.
Patients with chronic kidney disease are at an increased risk of venous thromboembolism (VTE). The factor Xa inhibitor rivaroxaban has been shown to provide similar efficacy and a lower risk of bleeding compared with vitamin K antagonists for the treatment and prevention of VTE. Rivaroxaban has been studied in patients with varying degrees of renal impairment, and this review summarizes current knowledge supporting its use in patients with severe renal impairment (creatinine clearance [CrCl] of 15 to < 30 mL/min) for the prevention, treatment, or prophylaxis of VTE. Clinical pharmacology studies have demonstrated an increase in rivaroxaban systemic exposure, factor Xa inhibition, and prothrombin time with decreasing renal function. These changes reach a plateau with comparable increases in exposure among individuals with moderate or severe renal impairment and end-stage renal disease. The clinical development program for the treatment and prevention of VTE as well as prophylaxis of deep vein thrombosis (DVT) following orthopedic surgery excluded patients with CrCl < 30 mL/min; however, a limited number of patients with severe renal impairment were enrolled. Efficacy outcomes in these patients with severe renal impairment were not meaningfully different from those of patients with higher levels of renal function. There was also no increase in the incidence of major bleeding with rivaroxaban in patients with CrCl < 30 mL/min. Taken together, these pharmacological and clinical data suggest that in patients with severe renal impairment, the approved dosages of rivaroxaban can be used in the treatment and prevention of VTE and for prophylaxis of DVT after hip or knee replacement surgery.
患有慢性肾病的患者发生静脉血栓栓塞症(VTE)的风险增加。因子 Xa 抑制剂利伐沙班在治疗和预防 VTE 方面与维生素 K 拮抗剂相比,显示出相似的疗效和较低的出血风险。利伐沙班已在不同程度肾功能损害的患者中进行了研究,本综述总结了支持其在严重肾功能损害(肌酐清除率 [CrCl] 为 15 至 <30 mL/min)患者中用于预防、治疗或预防 VTE 的现有知识。临床药理学研究表明,随着肾功能的下降,利伐沙班的全身暴露、因子 Xa 抑制和凝血酶原时间增加。在中度或重度肾功能损害和终末期肾病患者中,这些变化达到平台期,暴露量的增加具有可比性。VTE 的治疗和预防以及骨科手术后深静脉血栓形成(DVT)的预防临床开发项目排除了 CrCl <30 mL/min 的患者;然而,纳入了少数严重肾功能损害的患者。这些严重肾功能损害患者的疗效结果与肾功能较高的患者没有明显差异。CrCl <30 mL/min 的患者使用利伐沙班也没有增加主要出血的发生率。综上所述,这些药理学和临床数据表明,在严重肾功能损害的患者中,利伐沙班的批准剂量可用于治疗和预防 VTE,以及髋关节或膝关节置换术后 DVT 的预防。