Development and comparison of a new personalized warfarin stable dose prediction algorithm in Chinese patients undergoing heart valve replacement.

Abstract

BACKGROUND:

Pharmacogenetics-based algorithms would be especially desirable for patients undergoing heart valve replacement (HVR), who are particularly sensitive to warfarin during the initial treatment phase following surgery. We aimed to derive a warfarin dosing algorithm from data of Chinese patients undergoing HVR, and to compare it with previously published dosing algorithms as applied to our HVR patients.

METHODS:

641 Chinese HVR patients on stable maintenance dose of warfarin were enrolled from a single clinic site. Data of 321 patients were used to derive a warfarin dosing algorithm using stepwise multiple linear regression analysis. Previously published algorithms were selected from Pubmed database for comparison. The performance of all the algorithms was characterized according to mean absolute error (MAE) and percentage of predicted doses falling within +/- 20% of clinically observed doses (percentage of ideal prediction) in the other 320 patients.

RESULTS:

The newly developed algorithm included eight factors: VKORC1-1639G > A, CYP2C9*3, BSA, age, number of increasing INR drugs, smoking habit, preoperative stroke history and hypertension. Our algorithm accounted for 56.4% of variations in the inter-patient warfarin stable doses. All the algorithms showed better performance in a medium-dose (1.88-4.38 mg/day) and high-dose (> or = 4.38 mg/day) groupings than in a low-dose (< or = 1.88 mg/day) grouping. Compared with the 14 previously published algorithms, our algorithm had the lowest MAE (-0.07 mg/day) and the highest percentage of ideal prediction (62.8%) in the total validation cohort.

CONCLUSIONS:

Our warfarin dosing algorithm is potentially useful for patients whose population profiles are similar to those of our patients.

• Authors: S L Tan, Z Li, G B Song, L M Liu, W Zhang, J Peng, T Zhang, F F Jia, G Zhou, H H Zhou, X M Zhou
• Journal: Die Pharmazie (Pharmazie) Vol. 67 Issue 11 Pg. 930-7 (Nov 2012) ISSN: 0031-7144 [Print] Germany
• PMID: 23210243 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Warfarin
• DNA
• CYP2C9 protein, human
• Cytochrome P-450 CYP2C9
• Aryl Hydrocarbon Hydroxylases

Topics

• Adolescent
• Adult
• Aged
• Algorithms
• Anticoagulants (administration & dosage)
• Aryl Hydrocarbon Hydroxylases (genetics)
• Asian People
• Cytochrome P-450 CYP2C9
• DNA (biosynthesis, genetics)
• Female
• Genotype
• Heart Valve Prosthesis Implantation (methods)
• Humans
• International Normalized Ratio
• Male
• Middle Aged
• Polymerase Chain Reaction
• Polymorphism, Single Nucleotide
• Precision Medicine
• Regression Analysis
• Reproducibility of Results
• Warfarin (administration & dosage)
• Young Adult