Plasma Concentrations of Direct Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation and Different Degrees of Obesity.

IF 4 2区医学 Q1 PHARMACOLOGY & PHARMACY

Clinical Pharmacokinetics Pub Date : 2025-03-01 Epub Date: 2025-02-12 DOI:10.1007/s40262-025-01474-8

Danilo Menichelli, Arianna Pannunzio, Erminia Baldacci, Vittoria Cammisotto, Valentina Castellani, Rosaria Mormile, Ilaria Maria Palumbo, Antonio Chistolini, Francesco Violi, Job Harenberg, Daniele Pastori, Pasquale Pignatelli

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引用次数: 0

Abstract

Background: Atrial fibrillation (AF) has multiple cardio-metabolic comorbidities, including obesity. The use of direct oral anticoagulants (DOACs) in patients with AF and obesity is still uncertain owing to the concern of possible ineffective DOAC plasma concentration. We evaluated the peak and trough plasma concentrations of DOACs in AF patients with different degrees of obesity.

Methods: Observational single-center study including patients with obesity and AF, between April 2022 and April 2024. Obesity was defined as body mass index (BMI) ≥ 30.0 kg/m². The 2-hour peak and trough DOAC plasma concentrations were assessed. Intake of DOAC was verified on site. Multivariable logistic regression analysis was used to assess the odds ratio (OR) and 95% confidence interval (95% CI) of factors associated with below-range trough concentration (BRTC) and below-range peak concentration (BRPC).

Results: In total, 160 patients (33.8% women) with a mean age of 73.2 ± 9.1 years were included. The median BMI was 32.3 kg/m². DOACs prescribed were apixaban (46.8%), rivaroxaban (21.8%), dabigatran (16.4%), and edoxaban (15.0%); 18.1% and 14.4% had BRTC and BRPC concentrations, respectively. Patients with BRTC were more frequently treated with edoxaban and dabigatran and had a higher BMI. On multivariable logistic regression analysis, dabigatran [hazard ratio (HR) 3.039, 95% CI 1.155-7.999, p = 0.024) and BMI ≥ II class (OR 2.625, 95% CI 1.087-6.335, p = 0.032] were associated with BRTC. Dabigatran (OR 4.296, 95% CI 1.523-12.120, p = 0.006) and apixaban (OR 0.277, 95% CI 0.096-0.802, p = 0.018) were directly and inversely associated with BRPC, respectively.

Conclusions: A nonnegligible proportion of patients with obesity and AF have below-range plasma concentrations of DOACs. Assessment of DOAC plasma concentration in obesity class ≥ II may be useful in these patients.

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非瓣膜性房颤与不同程度肥胖患者直接口服抗凝血药的血药浓度。

背景：房颤（AF）有多种心脏代谢合并症，包括肥胖。直接口服抗凝剂（DOACs）用于房颤合并肥胖患者仍不确定，因为担心DOAC血浆浓度可能无效。我们评估了不同程度肥胖的房颤患者DOACs的血药峰谷浓度。方法：观察性单中心研究，纳入肥胖和房颤患者，时间为2022年4月至2024年4月。肥胖定义为体重指数(BMI)≥30.0 kg/m2。测定2小时DOAC峰谷血药浓度。DOAC的摄入在现场进行了验证。采用多变量logistic回归分析评估与下限波谷浓度（BRTC）和下限峰值浓度（BRPC）相关因素的比值比（OR）和95%置信区间（95% CI）。结果：共纳入160例患者（女性33.8%），平均年龄73.2±9.1岁。BMI中位数为32.3 kg/m2。处方的doac为阿哌沙班（46.8%）、利伐沙班（21.8%）、达比加群（16.4%）和依多沙班（15.0%）；BRTC和BRPC浓度分别为18.1%和14.4%。BRTC患者使用依多沙班和达比加群治疗的频率更高，BMI也更高。多变量logistic回归分析显示，达比加群[风险比（HR） 3.039, 95% CI 1.155 ~ 7.999, p = 0.024]和BMI≥II级(OR 2.625, 95% CI 1.087 ~ 6.335, p = 0.032]与BRTC相关。达比加群（OR 4.296, 95% CI 1.523-12.120, p = 0.006）和阿哌沙班（OR 0.277, 95% CI 0.096-0.802, p = 0.018）分别与BRPC呈正相关和负相关。结论：肥胖和房颤患者血浆DOACs浓度低于范围的比例不可忽视。评估DOAC血浆浓度在肥胖≥II类患者可能是有用的。

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

Clinical Pharmacokinetics 医学-药学

CiteScore

8.80

自引率

4.40%

发文量

审稿时长

6-12 weeks

期刊介绍： Clinical Pharmacokinetics promotes the continuing development of clinical pharmacokinetics and pharmacodynamics for the improvement of drug therapy, and for furthering postgraduate education in clinical pharmacology and therapeutics. Pharmacokinetics, the study of drug disposition in the body, is an integral part of drug development and rational use. Knowledge and application of pharmacokinetic principles leads to accelerated drug development, cost effective drug use and a reduced frequency of adverse effects and drug interactions.