Warfarin dose management affects INR control

Background: Little is known about how patterns of warfarin dose management contribute to percentage time in the therapeutic International Normalized Ratio (INR) range (TTR). Objectives: To quantify the contribution of warfarin dose management to TTR and to define an optimal dose management strategy. Patients/methods: 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. Results: 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%). Conclusions: 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.