Optimal initial dose adjustment of warfarin in orthopedic patients.

Abstract

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.

• Authors: Petra A Lenzini, Gloria R Grice, Paul E Milligan, Susan K Gatchel, Elena Deych, Charles S Eby, R Stephen J Burnett, John C Clohisy, Robert L Barrack, Brian F Gage
• Journal: The Annals of pharmacotherapy (Ann Pharmacother) Vol. 41 Issue 11 Pg. 1798-804 (Nov 2007) ISSN: 1542-6270 [Electronic] United States
• PMID: 17911206 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anticoagulants
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Warfarin

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Algorithms
• Anticoagulants (administration & dosage, adverse effects, therapeutic use)
• Arthroplasty, Replacement, Hip
• Arthroplasty, Replacement, Knee
• Blood Loss, Surgical (prevention & control)
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• International Normalized Ratio
• Male
• Middle Aged
• Prospective Studies
• Pulmonary Embolism (prevention & control)
• Venous Thrombosis (prevention & control)
• Warfarin (administration & dosage, adverse effects, therapeutic use)