Peak and Trough Concentrations of Apixaban and Rivaroxaban in Adult Patients: A Systematic Review and Meta-Analysis.

IF 5.5 2区医学 Q1 HEMATOLOGY Journal of Thrombosis and Haemostasis Pub Date : 2025-01-09 DOI:10.1016/j.jtha.2024.12.032

Christian Andrew Almalbis, Adyani Md Redzuan, Chester Paul Andrada, Nicole Ann Gonzaga, Shamin Mohd Saffian

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Abstract

Background: Apixaban and rivaroxaban are factor Xa inhibitors commonly used for treatment of venous thromboembolism and stroke prevention in patients with atrial fibrillation. While routine monitoring of their concentrations is not recommended, but it may be beneficial in certain situations. Expected peak and trough concentrations remain poorly understood, with most data derived from small studies OBJECTIVES: To establish the average peak and trough concentrations of apixaban and rivaroxaban from real-world studies.

Methods: PubMed, Scopus, and Web of Science were searched until October 2023 for observational studies reporting apixaban and rivaroxaban concentrations. Meta-regression was used to examine factors influencing these concentrations.

Results: Sixteen studies involving 1054 apixaban and 1321 rivaroxaban patients were pooled using random-effects model. Mean apixaban peak concentrations were 157 ng/mL (95% CI, 127-187) for 2.5 mg and 228 ng/mL (95% CI, 204-252) for 5 mg, with trough concentrations of 77 ng/mL (95% CI, 56-98) and 113 ng/mL (95% CI, 101-124), respectively. Mean rivaroxaban peak concentrations were 168 ng/mL (95% CI, 104-232) for 10 mg, 225 ng/mL (95% CI, 192-257) for 15 mg, and 229 ng/mL (95% CI, 193-264) for 20 mg, with trough concentrations of 23 ng/mL (95% CI, 13-32), 31 ng/mL (95% CI, 26-36), and 36 ng/mL (95% CI, 25-47), respectively. Meta-regression revealed age and creatinine clearance correlated with apixaban peak concentrations. Creatinine clearance correlated with apixaban and rivaroxaban trough concentrations.

Conclusions: The pooled mean concentrations align with expected concentration ranges reported in different pharmacokinetic studies.

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阿哌沙班和利伐沙班在成人患者中的峰谷浓度：一项系统回顾和荟萃分析。

背景：阿哌沙班和利伐沙班是Xa因子抑制剂，常用于房颤患者静脉血栓栓塞的治疗和卒中预防。虽然不建议对其浓度进行常规监测，但在某些情况下可能是有益的。预期的峰谷浓度仍然知之甚少，大多数数据来自小型研究目的：从现实世界的研究中建立阿哌沙班和利伐沙班的平均峰谷浓度。方法：PubMed、Scopus和Web of Science检索到2023年10月之前报告阿哌沙班和利伐沙班浓度的观察性研究。meta回归分析了影响这些浓度的因素。结果：采用随机效应模型共纳入16项研究，涉及1054例阿哌沙班患者和1321例利伐沙班患者。阿哌沙班平均峰浓度为2.5 mg时为157 ng/mL (95% CI, 127-187)， 5 mg时为228 ng/mL (95% CI, 204-252)，谷浓度分别为77 ng/mL （95% CI, 56-98）和113 ng/mL （95% CI, 101-124）。利伐沙班平均峰浓度为10 mg时为168 ng/mL (95% CI, 104-232)， 15 mg时为225 ng/mL (95% CI, 192-257)， 20 mg时为229 ng/mL (95% CI, 193-264)，谷浓度分别为23 ng/mL (95% CI, 13-32), 31 ng/mL （95% CI, 26-36）和36 ng/mL （95% CI, 25-47）。meta回归显示年龄和肌酐清除率与阿哌沙班峰值浓度相关。肌酐清除率与阿哌沙班和利伐沙班谷浓度相关。结论：合并的平均浓度与不同药代动力学研究报告的预期浓度范围一致。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Thrombosis and Haemostasis 医学-外周血管病

CiteScore

24.30

自引率

3.80%

发文量

321

审稿时长

1 months

期刊介绍： The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community. Types of Publications: The journal publishes a variety of content, including: Original research reports State-of-the-art reviews Brief reports Case reports Invited commentaries on publications in the Journal Forum articles Correspondence Announcements Scope of Contributions: Editors invite contributions from both fundamental and clinical domains. These include: Basic manuscripts on blood coagulation and fibrinolysis Studies on proteins and reactions related to thrombosis and haemostasis Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.