Using highly variable warfarin dosing to identify patients at risk for adverse events

We used a database of over 4, 000 patients who received oral anticoagulation in community practice between 2000-2002. We reviewed the charts of 168 patients with large warfarin dose variation and agreed on 18 risk factor definitions for high dose variability. We identified 109 patients with the highest dose variability (cases), as measured by coefficient of variation (CoV, SD/mean). We matched each case to two controls with low dose variability. Then, we examined all 327 charts, blinded to case/control status, to identify the presence or absence of the 18 risk factors for dose variability. We performed a multivariable analysis to identify independent predictors of high CoV. We also compared anticoagulation control, as measured by percent time in therapeutic range (TTR), and rates of adverse events between groups.CoV corresponded with other measures of anticoagulation control. TTR was 53% among cases and 79% among controls (p < 0.001). CoV also predicted adverse events. Six cases experienced a major hemorrhage versus 1 control (p < 0.001) and 3 cases had a thromboembolic event versus 0 control patients (p = 0.04). Independent predictors of high dose variability included hospitalization (OR = 21.3), decreased oral intake (OR = 12.2), use of systemic steroids (OR = 6.1), acetaminophen (OR = 4.0) and antibiotics (OR = 2.7; p < 0.05 for all).CoV can be used to identify patients at risk for poor anticoagulation control and adverse events. This new measure has the potential to identify patients at high risk before they suffer adverse events.Warfarin is the standard anticoagulation treatment for atrial fibrillation, venous thromboembolism (VTE), and mechanical heart valves [1-4]. Close monitoring of the International Normalized Ratio (INR) is required due to the drug's very narrow therapeutic window. Many factors can affect INR levels [1,5,6]. Values must be kept within range to reduce the risk of hemorrhage [7,8] and the risk of developing thromboembolism [9]. Previous stu