Decreasing warfarin sensitivity during the first three months after heart valve surgery: Implications for dosing

INTRODUCTION: Vitamin K antagonists are prescribed to prevent thromboembolic complications after heart valve surgery. In our experience, patients often show a progressive decrease in sensitivity to warfarin after surgery making it difficult to reach and maintain a therapeutic International Normalized Ratio (INR). We sought to confirm our clinical impression and to gather data for the development of a guide to dosing these patients. MATERIALS AND METHODS: In a large anticoagulation clinic, we retrospectively reviewed 200 patients who were on warfarin (target range of 2.0-3.0) during the first three months after valve surgery. Data on dosing and INR results were collected and time in therapeutic range (TTR) calculated. Controls were patients started on warfarin for atrial fibrillation. RESULTS: A steady increase in warfarin requirements was seen over the three months in patients with mechanical valves, bioprosthetic valves or valve repairs. The mean dose of warfarin increased by 26% while the mean INR decreased from 2.5 to 2.1. In contrast, both the mean dose of warfarin and the INR were stable in controls. TTR in patients after valve surgery was 48.5%, with 40.8% of time spent at an INR below 2.0. A dosing algorithm was modeled from the data in this patient group. CONCLUSIONS: Patients steadily become less sensitive to warfarin during the first months after heart valve surgery. This leads to subtherapeutic anticoagulation. A dosing algorithm that takes increasing requirements into account is proposed. This algorithm will need to be validated prospectively.