Predicting warfarin maintenance dose in patients with venous thromboembolism based on the response to a standardized warfarin initiation nomogram.
BACKGROUND
Polymorphisms in the VKORC1 and CYP2C9 genes influence warfarin requirements. It has been suggested that dosing algorithms incorporating them might outperform usual care. Standardized warfarin initiation nomograms are safe and effective and patients' responses to them could be used to predict warfarin requirements without the need for genetic testing.


OBJECTIVE
To develop a model to predict warfarin dose requirements based on the response to a standard nomogram without using genetic testing.


METHODS
We included 363 outpatients with acute venous thromboembolism who were started on treatment using a standardized warfarin nomogram and achieved a stable maintenance warfarin dose defined as a dose prescribed twice consecutively after two consecutive INR measurements between 2.0 and 3.0. Linear regression was used to derive equations predicting the maintenance dose and models were validated using non-parametric bootstrapping and tested in an independent cohort.


RESULTS
Three models were constructed for patients completing the nomogram until day 3 (warfarin dose (mg week(-1)) = Exp [2.737 + 1.896(INR(3)(-1))-0.008(Age)]; R2adj = 0.462), day 5 (warfarin dose (mg week(-1)) = Exp[2.261 + 2.412(INR(3)(-1)) -0.285(DeltaINR(5-3))]; R2adj = 0.603) and day 8 (warfarin dose (mg week(-1)) = Exp[1.574 + 1.788(INR(8)(-1)) + 0.024(cumulated warfarin dose until nomogram day 7)]; R2adj = 0.643), where Exp is the exponential function; INR3 and INR8 are the INR on days 3 or 8 of the nomogram, and DeltaINR(5-3) is the difference in the INR on days 5 and 3. All models were internally and externally validated and were accurate to within 25% of the actual dose in >60% of patients.


CONCLUSIONS
Maintenance warfarin dose can be accurately predicted using individual response to a standard warfarin initiation nomogram without the need for costly genetic testing.
Lazo-Langner
A
A
Division of Hematology, Department of Medicine, University of Western Ontario, London, ON, Canada.
Monkman
K
K
Kovacs
M J
MJ
D015331:Cohort Studies; D054796:Drug Dosage Calculations; D006801:Humans; D019934:International Normalized Ratio; D016014:Linear Models; D008962:Models, Theoretical; D049451:Nomograms; D012189:Retrospective Studies; D054556:Venous Thromboembolism / Q000188:drug therapy*; D014859:Warfarin / Q000008:administration & dosage*
D014859:Warfarin