Talerico Rosa, Pola Roberto, Klok Frederikus Albertus, Huisman Menno Volkert
Section of Internal Medicine and Thromboembolic Diseases, Department of Internal Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
IRCCS San Raffaele, Rome, Italy.
TH Open. 2024 Jan 8;8(1):e31-e41. doi: 10.1055/s-0043-1776989. eCollection 2024 Jan.
Patients at extremes of body weight are underrepresented in randomized controlled trials of direct-acting oral anticoagulants (DOACs). Therefore, their optimal anticoagulant treatment remains a topic of debate. The aim of this narrative review is to summarize the evidence on the pharmacokinetic and pharmacodynamic profile of DOACs for treating patients at extremes of body weight in venous thromboembolism (VTE) and in the prevention of cardioembolic stroke in nonvalvular atrial fibrillation (NVAF). A literature search was conducted in the main bibliographic databases, and the most relevant reviews and original articles on the topic were selected. Although data in these patient groups are limited, apixaban and rivaroxaban show a favorable pharmacokinetic and pharmacodynamic profile in obese VTE treatment and NVAF patients and, in the case of apixaban, also in underweight patients. In particular, these drugs demonstrated comparable efficacy and safety to standard therapy. Very few data were available for dabigatran and edoxaban; the latter drug was safer at a lower dose, mainly in underweight patients. Our findings are in line with the last International Society of Haemostasis and Thrombosis position paper and European Heart Rhythm Association 2021 practical guide, suggesting the use of apixaban and rivaroxaban in morbidly obese patients (>120 kg or body mass index ≥40 kg/m ) and the reduced dosage of edoxaban in low-weight patients. Future studies should focus on large populations of patients at extremes of body weights to acquire more clinical and pharmacokinetic evidence on all available DOACs, especially those currently less investigated.
在直接作用口服抗凝剂（DOACs）的随机对照试验中，体重过轻或过重的患者代表性不足。因此，他们的最佳抗凝治疗仍是一个有争议的话题。本叙述性综述的目的是总结关于DOACs在治疗体重过轻或过重的静脉血栓栓塞（VTE）患者以及预防非瓣膜性心房颤动（NVAF）的心源性卒中方面的药代动力学和药效学特征的证据。在主要的文献数据库中进行了文献检索，并选择了关于该主题最相关的综述和原始文章。尽管这些患者群体的数据有限，但阿哌沙班和利伐沙班在肥胖VTE治疗和NVAF患者中显示出良好的药代动力学和药效学特征，就阿哌沙班而言，在体重过轻的患者中也是如此。特别是，这些药物显示出与标准治疗相当的疗效和安全性。关于达比加群和依度沙班的数据非常少；后者在较低剂量时更安全，主要是在体重过轻的患者中。我们的研究结果与国际血栓与止血学会的最新立场文件以及欧洲心律协会2021年实用指南一致，建议在病态肥胖患者（>120 kg或体重指数≥40 kg/m²）中使用阿哌沙班和利伐沙班，并在体重较轻的患者中减少依度沙班的剂量。未来的研究应关注大量体重过轻或过重的患者群体，以获取关于所有可用DOACs的更多临床和药代动力学证据，尤其是那些目前研究较少的药物。
