Warfarin dose management affects INR control

Little is known about how patterns of warfarin dose management contribute to percentage time in the therapeutic International Normalized Ratio (INR) range (TTR).

To quantify the contribution of warfarin dose management to TTR and to define an optimal dose management strategy.

We enrolled 3961 patients receiving warfarin from 94 community-based clinics. We derived and validated a model for the probability of a warfarin dose change under various conditions. For each patient, we computed an observed minus expected (O - E) score, comparing the number of dose changes predicted by our model to the number of changes observed. We examined the ability of O - E scores to predict TTR, and simulated various dose management strategies in the context of our model.

Patients were observed for a mean of 15.2 months. Patients who deviated the least from the predicted number of dose changes achieved the best INR control (mean TTR 70.1% unadjusted); patients with greater deviations had lower TTR (65.8% and 62.0% for fewer and more dose changes respectively, Bonferroni-adjusted P < 0.05/3 for both comparisons). On average, clinicians in our study changed the dose when the INR was 1.8 or lower/3.2 or higher (mean TTR: 68%); optimal management would have been to change the dose when the INR was 1.7 or lower/3.3 or higher (predicted TTR: 74%).

Our observational study suggests that INR control could be improved considerably by changing the warfarin dose only when the INR is 1.7 or lower/3.3 or higher. This should be confirmed in a randomized trial.