Prediction of the warfarin maintenance dose after completion of the 10 mg initiation nomogram: do we really need genotyping?
BACKGROUND
Initiation of warfarin therapy is complicated by its narrow therapeutic index and inter-patient dose-effect variability. A '10-mg nomogram' warfarin initiation protocol permits safe therapeutic anticoagulation in outpatients started on warfarin. We aimed to develop a safe and effective warfarin maintenance dose prediction tool in these patients.


METHODS
Baseline potential predictor variables were collected on a retrospective cohort of outpatients initiated on warfarin for venous thromboembolism treatment. The primary outcome was the warfarin maintenance dose, defined as mean warfarin dose over the last 10 days of the first month of warfarin treatment. Univariate and multivariate analyses were performed to determine which baseline variables were warfarin maintenance dose predictors. An independent cohort of patients validated the derived warfarin maintenance dose prediction rule.


RESULTS
Patient's age and weight, cumulative dose of warfarin over the first week of induction and international normalized ratio (INR) on days 3, 5 and 8 were statistically significant predictors of the warfarin maintenance dose. Our final prediction rule reads: maintenance dose (in mg) = 2.5 + 10% of the first week cumulative dose - INR value at day 8 + 1.5 if INR was below 2.0 at day 5. In the validation cohort, the predicted dose was strongly correlated with the actual maintenance dose (r = 0.88, P < 0.0001). The mean difference between observed and predicted dose was not clinically significant: -0.1 +/- 1.1 mg.


CONCLUSIONS
In outpatients initiated on warfarin using a '10-mg nomogram', a simple prediction rule can accurately predict warfarin maintenance dose. Prospective studies employing the rule are indicated.
Le Gal
G
G
Thrombosis Program, Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
Carrier
M
M
Tierney
S
S
Majeed
H
H
Rodger
M
M
Wells
P S
PS
D000284:Administration, Oral; D000328:Adult; D000367:Age Factors; D000368:Aged; D000553:Ambulatory Care; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001777:Blood Coagulation / Q000187:drug effects*; D001835:Body Weight; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005838:Genotype; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D049451:Nomograms; D010641:Phenotype; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D054556:Venous Thromboembolism / Q000097:blood / Q000188:drug therapy*; D014812:Vitamin K / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
D000925:Anticoagulants; D014812:Vitamin K; D014859:Warfarin