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Int J Med Sci 2012; 9(6):472-479. doi:10.7150/ijms.4637

Research Paper

Clinical Application of Pharmacogenetic-Based Warfarin-Dosing Algorithm in Patients of Han Nationality after Rheumatic Valve Replacement: A Randomized and Controlled Trial

MingSong Wang1#, XiLong Lang2#, ShiTao Cui3✉, Ke Fei4✉, LiangJian Zou2, Jia Cao5, LiangXu Wang5, ShengHui Zhang5, XinTian Wu5, YiLing Wang5, Qiang Ji6✉

1. Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
2. Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
3. Department of Emergency Surgery, Ninth People's Hospital of Shanghai Jiaotong University School of Medicine, Shanghai 200072, P.R. China.
4. Department of Thoracic Surgery, Pulmonary Hospital of Tongji University, Shanghai 200433, P.R. China.
5. Department of Thoracic Cardiovascular Surgery, Tenth People's Hospital of Tongji University, Shanghai 200072, P.R. China.
6. Department of Thoracic Cardiovascular Surgery, Tongji Hospital of Tongji University, Shanghai 200065, P.R. China.
# Contributed equally as the co-first author.

Abstract

Background The polymorphisms of VKORC1 and CYP2C9 play increasingly important roles in the inter-individual variability in warfarin dose. This study aimed to evaluate the feasibility of clinical application of pharmacogenetic-based warfarin-dosing algorithm in patients of Han nationality with rheumatic heart disease after valve replacement in a randomized and controlled trial. Methods One hundred and one consecutive patients of Han nationality with rheumatic heart disease undergoing valve surgery were enrolled and randomly assigned to an experimental group (n=50, based on CYP2C9 and VKORC1 genotypes, pharmacogenetic-based “predicted warfarin dose” for 3 days and then was adjusted to INR until stable warfarin maintenance dose) or a control group (n=51, 2.5mg/d for 3 days and then was adjusted to INR until stable warfarin maintenance dose). All included patients were followed for 50 days after initiation of warfarin therapy. The primary end-point was the time to reach a stable warfarin maintenance dose. Results During the follow-up, 84.0% patients in the experimental group and 58.8% patients in the control group received warfarin maintenance dose. Compared with control group, patients in the experimental group had shorter mean time elapse from initiation of warfarin therapy until warfarin maintenance dose (27.5±1.8 d versus 34.7±1.8 d, p<0.001). Cox regression revealed that group (HR for experimental versus control group: 1.568, 95%CI 1.103-3.284) and age were two significant variables related to the time elapse from initiation of warfarin therapy until warfarin maintenance dose. The predicted warfarin maintenance dose was prominently correlated with the actual warfarin maintenance dose (r=0.684, p<0.001). Conclusion: Based on CYP2C9 and VKORC1 genotypes, the pharmacogenetic-based warfarin-dosing algorithm may shorten the time elapse from initiation of warfarin therapy until warfarin maintenance dose. It is feasible for the clinical application of the pharmacogenetic-based warfarin-dosing algorithm in patients of Han nationality with rheumatic heart disease after valve replacement.

Keywords: Pharmacogenetics, Individualized warfarin therapy, Rheumatic valve surgery, Trial.

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How to cite this article:
Wang M, Lang X, Cui S, Fei K, Zou L, Cao J, Wang L, Zhang S, Wu X, Wang Y, Ji Q. Clinical Application of Pharmacogenetic-Based Warfarin-Dosing Algorithm in Patients of Han Nationality after Rheumatic Valve Replacement: A Randomized and Controlled Trial. Int J Med Sci 2012; 9(6):472-479. doi:10.7150/ijms.4637. Available from http://www.medsci.org/v09p0472.htm