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苯丙香豆素剂量需求、剂量稳定性及在伴有和多态性的老年患者中的治疗窗时间

Phenprocoumon Dose Requirements, Dose Stability and Time in Therapeutic Range in Elderly Patients With and Polymorphisms.

作者信息

Schneider Katharina Luise, Kunst Melanie, Leuchs Ann-Kristin, Böhme Miriam, Weckbecker Klaus, Kastenmüller Kathrin, Bleckwenn Markus, Holdenrieder Stefan, Coch Christoph, Hartmann Gunther, Stingl Julia Carolin

机构信息

Research Division, Federal Institute for Drugs and Medical Devices, Bonn, Germany.

Centre for Translational Medicine, Medical Faculty of the University of Bonn, Bonn, Germany.

出版信息

Front Pharmacol. 2020 Jan 28;10:1620. doi: 10.3389/fphar.2019.01620. eCollection 2019.

Abstract

BACKGROUND

Dose requirements of vitamin K antagonists are associated with and , but, compared to warfarin, less data is available about phenprocoumon. Furthermore, the effects on dose stability and anticoagulation quality are still unclear.

METHODS

Aim was to scrutinize phenprocoumon dose requirements, dose stability and anticoagulation quality in association to and in a natural cohort of elderly primary care patients. As a subgroup within the IDrug study, phenprocoumon treated patients with at least two INR values within three months before enrollment (n = 209) were analyzed concerning average weekly dose, standard deviation of weekly dose (intra-subject variability), constant dose (yes/no), average INR and TTR grouped by and (and combinations).

RESULTS

Average weekly dose per patient was 14.4 ± 5.3 mg, 11.9 ± 4.0 mg and 11.2 ± 4.3 mg in wildtypes, and carriers (p < .0001) and 16.0 ± 4.2 mg, 13.3 ± 5.1 mg and 8.0 ± 2.7 mg per week in CC, CT and TT genotypes, respectively (p < .0001). Significant differences concerning intra-subject variability were detected among all groups (p < .0001) with the smallest variability in carriers. TTR medians were 75.4%, 79.4% and 100% in wildtypes, and carriers, respectively (p = 0.0464). The proportion of patients with perfect control was highest among carriers, but this result was not significant (p = 0.0713).

DISCUSSION

Our analyses support the results of previous investigations regarding genotype-associated dose requirements and raise the hypothesis that dose stability and anticoagulation quality may be increased in carriers. However, our data should be treated cautiously due to the small sample size.

CLINICAL TRIAL REGISTRATION

German Clinical Trials Register, identifier DRKS00006256.

摘要

背景

维生素K拮抗剂的剂量需求与[具体因素1]和[具体因素2]相关,但与华法林相比,关于苯丙香豆素的数据较少。此外,其对剂量稳定性和抗凝质量的影响仍不明确。

方法

目的是在一组老年初级保健患者的自然队列中,研究苯丙香豆素的剂量需求、剂量稳定性和抗凝质量与[具体因素1]和[具体因素2]的关系。作为IDrug研究的一个亚组,对在入组前三个月内有至少两个国际标准化比值(INR)值的苯丙香豆素治疗患者(n = 209),按[具体因素1]和[具体因素2](及组合)分组,分析其平均每周剂量、每周剂量的标准差(个体内变异性)、固定剂量(是/否)、平均INR和治疗窗内时间百分比(TTR)。

结果

野生型、[具体基因1]和[具体基因2]携带者患者的平均每周剂量分别为14.4±5.3毫克、11.9±4.0毫克和11.2±4.3毫克(p <.0001),而CC、CT和TT基因型患者的平均每周剂量分别为16.0±4.2毫克、13.3±5.1毫克和8.0±2.7毫克(p <.0001)。在所有组中均检测到个体内变异性存在显著差异(p <.0001),其中[具体基因1]携带者的变异性最小。野生型、[具体基因1]和[具体基因2]携带者的TTR中位数分别为75.4%、79.4%和100%(p = 0.0464)。[具体基因1]携带者中抗凝控制良好的患者比例最高,但该结果无统计学意义(p = 0.0713)。

讨论

我们的分析支持了先前关于基因型相关剂量需求的研究结果,并提出了[具体基因1]携带者可能提高剂量稳定性和抗凝质量的假设。然而,由于样本量小,我们的数据应谨慎对待。

临床试验注册

德国临床试验注册中心,标识符DRKS00006256。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba5c/6997201/b83a0c90993e/fphar-10-01620-g001.jpg

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