title: The potential clinical and economic outcomes of pharmacogenetics-oriented management of warfarin therapy - a decision analysis.
abstract: Variant cytochrome P450 (CYP) 2C9 genotypes are associated with low maintenance dose requirement of warfarin therapy and increased risk of major bleeding events. The objective of the present study was to evaluate the potential clinical and economic outcomes of using CYP2C9 genotype data to guide the management of anticoagulation therapy and to identify influential factors affecting the cost-effectiveness of this treatment scheme. A decision tree was designed to simulate, over 12 months, the clinical and economic outcomes of patients newly started on warfarin associated with two alternatives: (1) no genotyping (non-genotyped group) and (2) CYP2C9 genotyping prior to initiation of warfarin therapy (genotyped group). Non-genotyped group patients would receive standard care of an anticoagulation clinic (AC). In the genotyped group, patients with at least one variant CYP2C9 allele would receive intensified anticoagulation service. Most of the clinical probabilities were derived from literature. The direct medical costs were estimated from the Diagnosis-Related Group charges and from literature. The total number of events and the direct medical cost per 100 patient-years in the genotyped and non-geno-typed groups were 9.58 and USD155,700, and, 10.48 and USD 150,500, respectively. The marginal cost per additional major bleeding averted in the genotyped group was USD 5,778. The model was sensitive to the variation of the cost and reduction of bleeding rate in the intensified anticoagulation service. In conclusion, the pharmacogenetics-oriented management of warfarin therapy is potentially more effective in preventing bleeding with a marginal cost. The cost-effectiveness of this treatment scheme depends on the relative cost and effectiveness of a pharmacogenetics-oriented intensified anticoagulation service comparing to the standard AC care.
authors.affiliation: Centre for Pharmacoeconomics Research, School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong Shatin, N.T., Hong Kong, China. joyceyou@cuhk.edu.hk
authors.forename: Joyce H S
authors.initials: JH
authors.lastname: You
authors.forename: Fredric W H
authors.initials: FW
authors.lastname: Chan
authors.forename: Raymond S M
authors.initials: RS
authors.lastname: Wong
authors.forename: Gregory
authors.initials: G
authors.lastname: Cheng
mesh_terms: D000465:Algorithms; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D003362:Cost-Benefit Analysis; D065729:Cytochrome P-450 CYP2C9; D003657:Decision Making; D016903:Drug Monitoring; D005838:Genotype; D006470:Hemorrhage / Q000191:economics; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods*; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage* / Q000191:economics* / Q000493:pharmacokinetics
chemical_list: D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases