College of Pharmacy, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, Nebraska.
Semin Respir Crit Care Med. 2021 Apr;42(2):233-249. doi: 10.1055/s-0041-1723952. Epub 2021 Feb 18.
There are currently more than 7 million patients taking a direct oral anticoagulant (DOAC), with more new prescriptions per year than warfarin. Despite impressive efficacy and safety data for the treatment of venous thromboembolism, patients with obesity or advanced renal impairment represented a small portion of the patients enrolled in the phase 3 clinical trials. Therefore, to evaluate the potential use of DOACs in these special populations, clinicians need to have an understanding of the pharmacokinetics and pharmacodynamics of these agents in these settings. Since data from randomized controlled trials are limited, data from observational trials are helpful in gaining comfort with the use of DOACs in these special populations. Selecting the appropriate dose for each agent is imperative in achieving optimal patient outcomes. We provide an extensive review of the pharmacokinetics, pharmacodynamics, phase 3 clinical trials, and observational studies on the use of DOACs in patients with advanced renal impairment, obesity, or other weight-related special populations to provide clinicians with a comprehensive understanding of the data for optimal drug and dose selection.
目前有超过 700 万名患者正在服用直接口服抗凝剂(DOAC),每年的新处方数量超过华法林。尽管 DOAC 在治疗静脉血栓栓塞症方面具有令人印象深刻的疗效和安全性数据,但肥胖或晚期肾功能不全的患者在参与 3 期临床试验的患者中所占比例很小。因此,为了评估 DOAC 在这些特殊人群中的潜在用途,临床医生需要了解这些药物在这些情况下的药代动力学和药效学。由于随机对照试验的数据有限,观察性试验的数据有助于在这些特殊人群中使用 DOAC 时获得信心。为了实现最佳的患者结局,为每个药物选择合适的剂量至关重要。我们广泛回顾了 DOAC 在晚期肾功能不全、肥胖或其他与体重相关的特殊人群中的药代动力学、药效学、3 期临床试验和观察性研究,为临床医生提供了对数据的全面了解,以实现最佳药物和剂量选择。