印度尼西亚心血管疾病患者华法林给药算法的药效学建模：一种抗凝治疗的定制方法。

Pharmacodynamic Modeling of Warfarin Dosing Algorithm for Cardiovascular Patients in Indonesia: A Tailored Method to Anticoagulation Therapy.

作者信息

Putriana Norisca Aliza, Latarissa Irma Rahayu, Rusdiana Taofik, Rostinawati Tina, Akbar Mohammad Rizki

机构信息

Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia.

Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia.

出版信息

Drug Des Devel Ther. 2025 Jan 29;19:671-681. doi: 10.2147/DDDT.S497738. eCollection 2025.

DOI:10.2147/DDDT.S497738

PMID:39896937

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11787782/

Abstract

PURPOSE

Warfarin is an anticoagulant drug widely used for treating thromboembolism-related conditions. The main challenge with this drug is the high variability in patients response, which is influenced by both clinical, non-clinical, and genetic factors, such as , and . Therefore, this research aimed to evaluate the impact of clinical and genetic factors on warfarin dose adjustment and to develop a dosing algorithm for patients with cardiovascular disease.

PATIENTS AND METHODS

A total of 77 research subjects were selected using consecutive sampling based on the inclusion criteria of cardiac outpatients on warfarin for ≥3 months with PT-INR data, complete medical records, and willingness to participate. Exclusion criteria included vitamin K use and inability to follow up. Patients demographic data and clinical characteristics were collected from medical records. Blood samples were obtained for genetic testing of (sequencing). Statistical analyses included both bivariate and multivariate analyses (logistic regression) with a significance level set at <0.05.

RESULTS

Statistical analysis using the Kruskal-Wallis test showed that the CC, CT, and TT genotypes were significantly associated with warfarin dose (p = 0.02). Furthermore, the Mann-Whitney test results showed that gender did not have a significant relationship with warfarin dose (p = 0.16). The Spearman Rank correlation test showed that age (p = 0.02) and BMI (p = 0.03) had significant relationships with warfarin dose (p < 0.05). However, gender (p = 0.89) had no effect, while age (p = 0.01), BMI (p = 0.01), and genotype (p = 0.01) significantly influenced warfarin dose determination.

CONCLUSION

In conclusion, the combined contribution of age (8.76%), BMI (7.95%), and genotype (8.29%) to warfarin dose adjustment was 25%. The linear regression model for predicting warfarin dose was determined to be y = 12.736-0.16age + 0.55BMI + 3.55*genotype, where 1 = CC, 2 = CT, and 3 = TT.

摘要

目的

华法林是一种广泛用于治疗血栓栓塞相关病症的抗凝药物。使用这种药物的主要挑战在于患者反应的高度变异性，这受到临床、非临床和遗传因素的影响，例如、和。因此，本研究旨在评估临床和遗传因素对华法林剂量调整的影响，并为心血管疾病患者制定给药算法。

患者与方法

根据心脏门诊患者服用华法林≥3个月且有PT-INR数据、完整病历记录以及愿意参与的纳入标准，采用连续抽样的方法共选取了77名研究对象。排除标准包括使用维生素K以及无法进行随访。从病历记录中收集患者的人口统计学数据和临床特征。采集血样进行（测序）的基因检测。统计分析包括双变量分析和多变量分析（逻辑回归），显著性水平设定为<0.05。

结果

使用Kruskal-Wallis检验进行的统计分析表明，CC、CT和TT基因型与华法林剂量显著相关（p = 0.02）。此外，Mann-Whitney检验结果表明，性别与华法林剂量无显著关系（p = 0.16）。Spearman秩相关检验表明，年龄（p = 0.02）和BMI（p = 0.03）与华法林剂量有显著关系（p < 0.05）。然而，性别（p = 0.89）无影响，而年龄（p = 0.01）、BMI（p = 0.01）和基因型（p = 0.01）对华法林剂量的确定有显著影响。