Brockmüller Christine, Meid Andreas D, Senges Jochen, Hochadel Matthias, Haefeli Walter E, Stoll Felicitas
Internal Medicine IX - Department of Clinical Pharmacology and Pharmacoepidemiology, Medical Faculty Heidelberg, Heidelberg University Hospital, Heidelberg University, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
Institute for Myocardial Infarction Research, Ludwigshafen, Germany.
Clin Drug Investig. 2025 Jan;45(1):29-43. doi: 10.1007/s40261-024-01411-w. Epub 2024 Dec 12.
Oral anticoagulation in patients with atrial fibrillation is crucial to prevent thrombus formation in the heart, a major cause of ischemic stroke. The appropriate dose of direct oral anticoagulants (DOAC) - either standard or reduced dose - must be chosen individually in accordance with defined patient characteristics. However, a significant proportion of patients receive inappropriately low DOAC doses (underdosing). With a novel medication-based approach, this study aims to facilitate the identification of patients at risk of DOAC underdosing.
The prospective ARENA registry is a multi-centre study on patients with atrial fibrillation in Germany. Patients gave detailed information on medication, including over-the-counter preparations. Medication data were grouped according to the Anatomical Therapeutic Chemical (ATC) classification. In a bivariate analysis, the characteristics of patients on an appropriate versus inappropriate dose were compared (n = 866). To further evaluate variables for their association with underdosing, a model based on ATC third level medication data complemented with dose-adjustment criteria and validated clinical scores in all patients with complete information was built (n = 504).
In 15% of patients, an inappropriately low dose was found. The number of DOAC drug interactions, concomitant antiplatelet therapy and the total drug count were the most important predictors of DOAC underdosing. Mineral supplements and better health-related quality of life (HrQoL) were predictive of correct DOAC dosing, among others.
Medication-related data showed to be predictive of DOAC underdosing. Clinicians should check for inappropriately reduced DOAC doses, especially in patients undergoing antiplatelet therapy, polypharmacy and reduced HrQoL.
NCT02978248; date of registration: 30 November 2016.
心房颤动患者口服抗凝治疗对于预防心脏血栓形成至关重要，而心脏血栓形成是缺血性卒中的主要原因。必须根据明确的患者特征单独选择直接口服抗凝剂（DOAC）的合适剂量，即标准剂量或降低剂量。然而，相当一部分患者接受的DOAC剂量过低（剂量不足）。本研究旨在通过一种基于新型药物的方法，促进对有DOAC剂量不足风险患者的识别。
前瞻性ARENA注册研究是一项针对德国心房颤动患者的多中心研究。患者提供了详细的用药信息，包括非处方药制剂。用药数据根据解剖治疗学化学（ATC）分类进行分组。在双变量分析中，比较了接受合适剂量与不合适剂量患者的特征（n = 866）。为了进一步评估与剂量不足相关的变量，在所有具有完整信息的患者（n = 504）中，建立了一个基于ATC第三级用药数据并辅以剂量调整标准和经过验证的临床评分的模型。
在15%的患者中发现剂量过低。DOAC药物相互作用的数量、联合抗血小板治疗和药物总数是DOAC剂量不足的最重要预测因素。矿物质补充剂和较好的健康相关生活质量（HrQoL）等也是正确DOAC给药的预测因素。
与用药相关的数据显示可预测DOAC剂量不足。临床医生应检查DOAC剂量是否不适当降低，尤其是在接受抗血小板治疗、联合用药和HrQoL降低的患者中。
NCT02978248；注册日期：2016年11月30日。
