Laboratory and clinical outcomes of pharmacogenetic vs. clinical protocols for warfarin initiation in orthopedic patients

Background: Warfarin is commonly prescribed for prophylaxis and treatment of thromboembolism after orthopedic surgery. During warfarin initiation, out‐of‐range International Normalized Ratio (INR) values and adverse events are common. Methods: In orthopedic patients beginning warfarin therapy, we de...

Full description

Saved in:
Bibliographic Details
Published in:Journal of thrombosis and haemostasis 2008-10, Vol.6 (10), p.1655-1662
Main Authors: LENZINI, P. A., GRICE, G. R., MILLIGAN, P. E., DOWD, M. B., SUBHERWAL, S., DEYCH, E., EBY, C. S., KING, C. R., PORCHE‐SORBET, R. M., MURPHY, C. V., MARCHAND, R., MILLICAN, E. A., BARRACK, R. L., CLOHISY, J. C., KRONQUIST, K., GATCHEL, S. K., GAGE, B. F.
Format: Article
Language:English
Subjects:
Adult
Aged
Algorithms
anticoagulants
Arthroplasty - adverse effects
Arthroplasty - methods
Clinical Protocols - standards
dosing algorithm
Female
Humans
Male
Middle Aged
orthopedic surgery
pharmacogenetics
Pharmacogenetics - methods
Predictive Value of Tests
Premedication
Prospective Studies
Risk Factors
Thromboembolism - prevention & control
Treatment Outcome
warfarin
Warfarin - administration & dosage
Warfarin - adverse effects
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background: Warfarin is commonly prescribed for prophylaxis and treatment of thromboembolism after orthopedic surgery. During warfarin initiation, out‐of‐range International Normalized Ratio (INR) values and adverse events are common. Methods: In orthopedic patients beginning warfarin therapy, we developed and prospectively validated pharmacogenetic and clinical dose refinement algorithms to revise the estimated therapeutic dose after 4 days of therapy. Results: The pharmacogenetic algorithm used the cytochrome P450 (CYP) 2C9 genotype, smoking status, peri‐operative blood loss, liver disease, INR values and dose history to predict the therapeutic dose. The R2 was 82% in a derivation cohort (n = 86) and 70% when used prospectively (n = 146). The R2 of the clinical algorithm that used INR values and dose history to predict the therapeutic dose was 57% in a derivation cohort (n = 178) and 48% in a prospective validation cohort (n = 146). In 1 month of prospective follow‐up, the percent time spent in the therapeutic range was 7% higher (95% CI: 2.7–11.7) in the pharmacogenetic cohort. The risk of a laboratory or clinical adverse event was also significantly reduced in the pharmacogenetic cohort (Hazard Ratio 0.54; 95% CI: 0.30–0.97). Conclusions: Warfarin dose adjustments that incorporate genotype and clinical variables available after four warfarin doses are accurate. In this non‐randomized, prospective study, pharmacogenetic dose refinements were associated with more time spent in the therapeutic range and fewer laboratory or clinical adverse events. To facilitate gene‐guided warfarin dosing we created a non‐profit website, http://www.WarfarinDosing.org.
ISSN:1538-7933
1538-7836
1538-7836
DOI:10.1111/j.1538-7836.2008.03095.x