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RESEARCH REPORTS |
1 Research Statistician, Washington University in St. Louis, St. Louis, MO
2 Assistant Professor, Saint Louis College of Pharmacy, St. Louis
3 Clinical Pharmacist, Washington University in St. Louis
4 Research Patient Assistant, Washington University in St. Louis
5 Research Statistician, Washington University in St. Louis
6 Associate Professor of Pathology and Immunology, Washington University in St. Louis
7 Orthopaedic Surgeon, Vancouver Island Health Authority, Division of Orthopaedic Surgery, Adult Reconstructive Surgery, Vancouver, British Columbia, Canada
8 Associate Professor of Orthopaedic Surgery, Washington University in St. Louis
9 C & J Knight Distinguished Professor of Orthopaedic Surgery, Department of Orthopaedic Surgery, Washington University in St. Louis
10 Associate Professor of Medicine, Department of Medicine, Washington University in St. Louis
* To whom correspondence should be addressed. E-mail: bgage{at}im.wustl.edu.
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Abstract |
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BACKGROUND: Warfarin sodium is commonly prescribed for the prophylaxis and treatment of venous thromboembolism. Dosing algorithms have not been widely adopted because they require a fixed initial warfarin dose (eg, 5 mg) and are not tailored to other factors that may affect the international normalized ratio (INR).
OBJECTIVE: To develop an algorithm that could predict a therapeutic warfarin dose based on drug interactions, INR response after the initial warfarin doses, and other clinical factors.
METHODS: We used stepwise regression to quantify the relationship between these factors in patients beginning prophylactic warfarin therapy immediately prior to joint replacement. In the derivation cohort (n = 271), we separately modeled the therapeutic dose after 2 and 3 initial doses. We prospectively validated these 2 models in an independent cohort (n = 105).
RESULTS: About half of the therapeutic dose variability was predictable after 3 days of therapy: R2 was 53% in the derivation cohort and 42% in the validation cohort. INR response after 3 warfarin doses (INR3) inversely correlated with therapeutic dose (p < 0.001). Intraoperative blood loss transiently, but significantly, elevated the postoperative INR values. Other significant (p < 0.03) predictors were the first and second warfarin doses (+7% and +6%, respectively, per 1 mg), and statin use (-15.0%). The model derived after 2 warfarin doses explained 32% of the variability in therapeutic dose.
CONCLUSIONS: We developed and validated algorithms that estimate therapeutic warfarin doses based on clinical factors and INR response available after 2-3 days of warfarin therapy. The algorithms are implemented online at www.WarfarinDosing.org.
Key Words: anticoagulants, orthopedics, warfarin.
Reprints: Dr. Gage, Department of Medicine, Washington University in St. Louis, Campus Box 8005, 660 South Euclid Ave., St. Louis, MO 63110, fax 314/454-5554, bgage@im.wustl.edu
This article has been cited by other articles:
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  M. H. Eckman, J. Rosand, S. M. Greenberg, and B. F. Gage Cost-Effectiveness of Using Pharmacogenetic Information in Warfarin Dosing for Patients With Nonvalvular Atrial Fibrillation Ann Intern Med, January 20, 2009; 150(2): 73 - 83. [Abstract] [Full Text] [PDF]
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