Relationship between time spent at extreme International Normalized Ratios and time in therapeutic range with bleeding and thrombosis in warfarin-treated patients

PURPOSE: The relationship between the time spent at extreme International Normalized Ratios (INRs) and the time in the therapeutic range (TTR) with bleeding and thrombosis in warfarin-treated patients was examined. METHODS: Consecutive patients treated with warfarin for atrial fibrillation or for venous thrombosis who were managed by the anticoagulation management service or adult internal medicine clinic of a large, tertiary care, integrated health system between June 1, 2011, and October 9, 2012, were eligible for study inclusion. Data collected for the outcomes analysis included INRs and dates; current use of aspirin, clopidogrel, prasugrel, ticagrelor, ticlopidine, or nonsteroidal antiinflammatory drugs; and any clinically significant bleeding or thrombosis events identified. RESULTS: In the 837 patients who met the inclusion criteria, 636.5 patient-years of therapy were provided, of which 14.4 patient-years (2.26% of time) were spent at INRs of <1.5; 2.9 patient-years of therapy (0.45% of time) were spent at INRs of >4.5. The patient population had a mean individual TTR of 65%. The percentage of time at an INR of >4.5 was positively associated with an increased risk of major bleeding (p = 0.0085). The percentage of time spent with an INR of <1.5 was not associated with a significant increase in the risk of thrombosis. CONCLUSION: The percentage of time spent with an INR of >4.5 was associated with an increased risk of major bleeding in patients receiving warfarin for atrial fibrillation or for venous thrombosis at two outpatient clinics. The relationships between thrombosis risk and the TTR or the time spent at an INR of <1.5 were not significant, but the thromboembolic event rate was unusually low, as was the time spent at an INR of <1.5.