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A Randomized Trial of Two Intensities of Warfarin for the Prevention of Recurrent Thrombosis in Patients with Antiphospholipid Antibodies



A Randomized Trial of Two Intensities of Warfarin for the Prevention of Recurrent Thrombosis in Patients with Antiphospholipid Antibodies



Blood 100(11): Abstract No 555



Retrospective studies suggest that patients with antiphospholipid antibodies (APLA) have an increased risk of recurrent thromboembolism (TE) when treated with warfarin using a targeted international normalized ratio (INR) range of 2.0 to 3.0. As a result, it has been recommended that such patients receive warfarin administered to achieve an INR of more than 3.0. However, there are no prospective data which support the superior efficacy of this regimen, and it is likely to cause more bleeding. Hence, we performed a randomized, blinded clinical trial in which the risk of recurrent TE was compared in patients allocated to warfarin administered with a target INR of 2.0 to 3.0 ("standard intensity") or 3.1 to 4.0 ("high intensity"). Eligible patients had both persistently positive APLA (anticardiolipin antibody and/or lupus anticoagulant) and a history of TE. One hundred fourteen patients were enrolled between 01/98 and 04/01. Patients were followed for an average of 2.68 years. Two of 58 (3.4%) patients allocated to "standard intensity" warfarin and 6 of 56 (10.7%) patients allocated to "high intensity" warfarin suffered an objectively confirmed recurrent TE (hazard ratio (HR) 3.1, 95% CI 0.6 to 15). Patients with a history of arterial TE had an increased risk of recurrent TE in the "high intensity" arm (HR 3.1, 95% CI 0.3 to 30). Similarly, patients with systemic lupus erthymatosus, and those with a lupus anticoagulant were also at increased risk of recurrence when treated with "high intensity warfarin"(OR 3.9, 95% CI 0.2 to 236 and OR 2.3, 95% CI 0.3 to 26, respectively). Three patients allocated to "standard intensity" warfarin, and 4 allocated to "high intensity" warfarin suffered a major bleeding complication (HR 1.04, 95% CI 0.2 to 4.8). Thirteen patients allocated to "standard intensity" warfarin (none of whom suffered recurrence), and 21 allocated to "high intensity" warfarin (4 of whom suffered recurrence) discontinued study drug prior to the end of the study. We conclude that our results do not support the use of warfarin administered to achieve an INR of more than 3.0 for the secondary prevention of TE in patients with an APLA. As a result of this study, we recommend that such patients receive warfarin administered to achieve an INR value of 2.0 to 3.0.

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