Accuracy of an internationally validated genetic-guided warfarin dosing algorithm compared to a clinical algorithm in an Arab population

IF 3 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Current Problems in Cardiology Pub Date : 2024-09-22 DOI:10.1016/j.cpcardiol.2024.102865

Amr M. Fahmi , Ahmed El Bardissy , Mohamed Omar Saad , Amr Fares , Ahmed Sadek , Mohamed Nabil Elshafei , Asma Eltahir , Asmaa Mohamed , Hazem Elewa

{"title":"Accuracy of an internationally validated genetic-guided warfarin dosing algorithm compared to a clinical algorithm in an Arab population","authors":"Amr M. Fahmi , Ahmed El Bardissy , Mohamed Omar Saad , Amr Fares , Ahmed Sadek , Mohamed Nabil Elshafei , Asma Eltahir , Asmaa Mohamed , Hazem Elewa","doi":"10.1016/j.cpcardiol.2024.102865","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><div>To identify the impact of <em>CYP2C9*2, *3, VKORC1−1639 G>A</em> and <em>CYP4F2*3</em> on warfarin dose in an Arab population. To compare the accuracy of a clinical warfarin dosing (CWD) versus genetic warfarin dosing algorithms (GWD) during warfarin initiation.</div></div><div><h3>Methods</h3><div>A cohort of Arab patients newly starting on warfarin had their dose calculated using CWD published in <span><span>www.warfarindosing.org</span><svg><path></path></svg></span> and were followed for 1 month. Each patient provided a saliva sample. DNA was extracted, purified and genotyped for <em>VKORC−1639 G>A, CYP2C9*2, CYP2C9*3</em> and <em>CYP4F2*3</em>. After reaching warfarin maintenance dose, the dose was recalculated using the GWD and median absolute error (MAE) and the percentage of warfarin doses within 20% of the actual dose were calculated and compared for the two algorithms.</div></div><div><h3>Results</h3><div>The study enrolled 130 patients from 12 Arabian countries. Compared to those with wild type, carriers of reduced function alleles in <em>CYP2C9</em> required significantly lower median (IQR) warfarin weekly dose [24.5 (15.3) vs. 35 (29.8) mg/week, p=0.006]. With regards to <em>VKORC</em>, patients with AA genotype had a significantly lower median (IQR) weekly warfarin dose compared to AG and GG [21(10.5) vs 29.4 (21), p<0.001 for AA vs AG, p<0.001 for AA vs GG]. The MAE (IQR) for the weekly dose of the GWD was significantly lower compared to CWD [8.1 (10.5) vs 12.4 (12.6) (p<0.001)].</div></div><div><h3>Conclusion</h3><div><em>CYP2C9</em> and <em>VKORC1</em> variants are important determinants of warfarin dose in the Arab population. The use of the genetic and clinical factors led to better warfarin dose estimation when compared to clinical factors alone.</div></div>","PeriodicalId":51006,"journal":{"name":"Current Problems in Cardiology","volume":"49 12","pages":"Article 102865"},"PeriodicalIF":3.0000,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Problems in Cardiology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0146280624005000","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose

To identify the impact of CYP2C9*2, *3, VKORC1−1639 G>A and CYP4F2*3 on warfarin dose in an Arab population. To compare the accuracy of a clinical warfarin dosing (CWD) versus genetic warfarin dosing algorithms (GWD) during warfarin initiation.

Methods

A cohort of Arab patients newly starting on warfarin had their dose calculated using CWD published in www.warfarindosing.org and were followed for 1 month. Each patient provided a saliva sample. DNA was extracted, purified and genotyped for VKORC−1639 G>A, CYP2C9*2, CYP2C9*3 and CYP4F2*3. After reaching warfarin maintenance dose, the dose was recalculated using the GWD and median absolute error (MAE) and the percentage of warfarin doses within 20% of the actual dose were calculated and compared for the two algorithms.

Results

The study enrolled 130 patients from 12 Arabian countries. Compared to those with wild type, carriers of reduced function alleles in CYP2C9 required significantly lower median (IQR) warfarin weekly dose [24.5 (15.3) vs. 35 (29.8) mg/week, p=0.006]. With regards to VKORC, patients with AA genotype had a significantly lower median (IQR) weekly warfarin dose compared to AG and GG [21(10.5) vs 29.4 (21), p<0.001 for AA vs AG, p<0.001 for AA vs GG]. The MAE (IQR) for the weekly dose of the GWD was significantly lower compared to CWD [8.1 (10.5) vs 12.4 (12.6) (p<0.001)].

Conclusion

CYP2C9 and VKORC1 variants are important determinants of warfarin dose in the Arab population. The use of the genetic and clinical factors led to better warfarin dose estimation when compared to clinical factors alone.

查看原文本刊更多论文

国际验证的基因指导华法林剂量算法与临床算法在阿拉伯人群中的准确性比较

目的确定阿拉伯人群中 CYP2C9*2、*3、VKORC1-1639 G>A 和 CYP4F2*3 对华法林剂量的影响。比较临床华法林剂量算法（CWD）与基因华法林剂量算法（GWD）在华法林起始阶段的准确性。方法对一组新开始使用华法林的阿拉伯患者使用 www.warfarindosing.org 上发表的 CWD 计算其剂量，并随访 1 个月。每位患者提供一份唾液样本。提取、纯化 DNA 并对 VKORC-1639 G>A、CYP2C9*2、CYP2C9*3 和 CYP4F2*3 进行基因分型。在达到华法林维持剂量后，使用 GWD 重新计算剂量，计算并比较两种算法的中位绝对误差（MAE）和实际剂量 20% 以内的华法林剂量百分比。与野生型患者相比，CYP2C9减低功能等位基因携带者所需的华法林每周剂量中位数（IQR）明显降低[24.5（15.3）毫克/周 vs. 35（29.8）毫克/周，P=0.006]。就 VKORC 而言，与 AG 和 GG 相比，AA 基因型患者的华法林每周剂量中位数（IQR）明显较低 [21(10.5) vs 29.4 (21)，AA vs AG，p<0.001，AA vs GG，p<0.001]。结论在阿拉伯人群中，CYP2C9 和 VKORC1 变体是决定华法林剂量的重要因素。与单独使用临床因素相比，使用遗传因素和临床因素能更好地估算华法林剂量。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Current Problems in Cardiology 医学-心血管系统

CiteScore

4.80

自引率

2.40%

发文量

392

审稿时长

6 days

期刊介绍： Under the editorial leadership of noted cardiologist Dr. Hector O. Ventura, Current Problems in Cardiology provides focused, comprehensive coverage of important clinical topics in cardiology. Each monthly issues, addresses a selected clinical problem or condition, including pathophysiology, invasive and noninvasive diagnosis, drug therapy, surgical management, and rehabilitation; or explores the clinical applications of a diagnostic modality or a particular category of drugs. Critical commentary from the distinguished editorial board accompanies each monograph, providing readers with additional insights. An extensive bibliography in each issue saves hours of library research.