Objectives: The purpose of this study was to determine the optimal intensity of oral anticoagulation in patients who participated in a randomized trial of oral anticoagulants or aspirin after infrainguinal bypass graft surgery.
Methods: The distribution of patient-time spent in international normalized ratio (INR) classes of 0.5 INR unit was calculated assuming a linear change between successive measurements. INR-specific incidence rates of ischemic and hemorrhagic events were calculated as the ratio of the number of events at a certain INR category and the total patient-time spent in that class. The relationship between INR class and event rates was quantified by rate ratios calculated in a Poisson regression model.
Results: In 1326 patients (mean age, 69 years) 41,928 INR measurements were recorded in 1698 patient-years. Patients spent 50% of the total time within the target range of 3.0 to 4.5 INR. Most of the patient-time (60%) was spent between 2.5 and 3.5 INR. For each increasing class of 0.5 INR, the incidence of ischemic events (n = 154, INR data on event available in 49%) decreased by a factor of 0.97 (95% CI, 0.87-1.08). The incidence of major bleeding (n = 123, INR data on event available in 65%) increased significantly by a factor of 1.27 (95% CI, 1.19-1.34) for each increasing 0.5 INR category. The optimal target range was 3.0 to 4.0 INR, with an incidence of 3.8 events (0.9 ischemic and 2.9 hemorrhagic) per 100 patient-years.
Conclusions: The target range of 3.0 to 4.0 INR is the optimal range of achieved anticoagulation intensity and is safe for the prevention of ischemic events in patients after infrainguinal bypass graft surgery.