de Vries Tim A C, Mallick Imaad U, Bhagirath Vinai C, Eikelboom John W, Gomes Calvin, Yi Qilong, McGrath Sean, Hirsh Jack, Chan Noel C
Department of Clinical and Experimental Cardiology and Cardiothoracic Surgery, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
Amsterdam Cardiovascular Sciences, Heart Failure and Arrhythmias, Amsterdam, The Netherlands.
Thromb Haemost. 2025 Jun;125(6):563-573. doi: 10.1055/a-2446-1348. Epub 2024 Nov 21.
Although most patients with atrial fibrillation (AF) receiving a direct oral anticoagulant (DOAC) do not require drug concentration measurements, there are situations where such information could be useful. Existing guidance documents provide usual on-therapy ranges for drug concentrations, but these have important limitations.This is a systematic review and meta-analysis of studies reporting trough and peak levels of DOAC regimens approved for stroke prevention in AF. We used random effects models and the quantile estimation method to estimate the median and a usual on-therapy range (10 and 90 percentiles).Of 4,822 unique publications, 53 studies met eligibility (29,266 trough and 12,103 peak levels). Usual on-therapy ranges for trough levels were 38 to 155 and 58 to 206 ng/mL for apixaban 2.5 and 5 mg twice daily; 35 to 138 and 33 to 151 ng/mL for dabigatran 110 and 150 mg twice daily; 8 to 54 and 13 to 66 ng/mL for edoxaban 30 and 60 mg daily; and 16 to 74 and 19 to 72 ng/mL for rivaroxaban 15 and 20 mg daily. The corresponding range for peak levels were 96 to 251 and 132 to 343; 65 to 223 and 76 to 285; 57 to 219 and 127 to 407; 131 to 384, and 169 to 313 ng/mL, respectively.This systematic review and meta-analysis provides updated and more representative usual on-therapy ranges of DOAC levels in patients with AF.
尽管大多数接受直接口服抗凝剂（DOAC）治疗的心房颤动（AF）患者不需要进行药物浓度测量，但在某些情况下，此类信息可能会有所帮助。现有指导文件提供了药物浓度的常规治疗范围，但这些范围存在重要局限性。这是一项对报告经批准用于AF患者卒中预防的DOAC治疗方案谷值和峰值水平的研究进行的系统评价和荟萃分析。我们使用随机效应模型和分位数估计方法来估计中位数和常规治疗范围（第10和第90百分位数）。在4822篇独特的出版物中，有53项研究符合纳入标准（29266个谷值水平和12103个峰值水平）。阿哌沙班2.5毫克和5毫克每日两次的谷值水平常规治疗范围分别为38至155纳克/毫升和58至206纳克/毫升；达比加群110毫克和150毫克每日两次的谷值水平常规治疗范围分别为35至138纳克/毫升和33至151纳克/毫升；依度沙班30毫克和60毫克每日一次的谷值水平常规治疗范围分别为8至54纳克/毫升和13至66纳克/毫升；利伐沙班15毫克和20毫克每日一次的谷值水平常规治疗范围分别为16至74纳克/毫升和19至72纳克/毫升。相应的峰值水平范围分别为96至251纳克/毫升和132至343纳克/毫升；65至223纳克/毫升和76至285纳克/毫升；57至219纳克/毫升和127至407纳克/毫升；131至384纳克/毫升和169至313纳克/毫升。这项系统评价和荟萃分析提供了AF患者DOAC水平更新的、更具代表性的常规治疗范围。
