Summary
Warfarin induction is accomplished by titrating dosage to coagulation test results.
Algorithms can guide this process but not identify the starting dose. We hypothesized
that an initial warfarin dose approximating the maintenance value would safely enhance
rapidity of induction. In a randomized trial we compared a fixed-dose to a maintenance-dose
strategy for beginning warfarin therapy. To predict the maintenance dose among patients
with differing warfarin requirements we performed regression analysis on clinical
factors derived from chart review. Four community hospitals supplied records for retrospective
analysis. The prospective trial was conducted in one, a 350-bed teaching institution.
A sample of inpatients anti-coagulated during 1998 formed the development set for
retrospective study; a 1999 sample formed the validation set. A one-year trial recruited
consecutive eligible inpatients initiated on warfarin. We randomly assigned patients
to a first warfarin dose calculated using our regression formula or fixed at 5 mg.
All patients’ subsequent doses were determined (as a percentage of initial) from coagulation
testing. We compared days to anticoagulation, hospitalized hours, complications, and
activity of factor II and protein C in a patient sample at intervals after induction.
Weight, age, serum albumin, and presence of malignancy explained 25-30% of variance
in maintenance dose. Ninety patients (44 calculated-dose and 46 standard-dose) evaluated
in the clinical trial. Mean time to anticoagulation (among patients achieving anticoagulation)
was 4.2 and 5.0 days, respectively (p = 0.007). We observed no significant differences
in other endpoints. Individualized initial dosing may safely hasten war-farin induction.
Keywords
Warfarin - randomized trials - dosing algorithms
