A Prospective Study on Warfarin Management Post Heart Valve Replacement or Heart Valve Repair Surgery

For unknown reasons, post mechanical heart valve surgery, patients have an immediate post-operative warfarin sensitivity about 50% highter than normal, taking approximately 12 weeks to normalise post operatively. Routinely, post-mechanical heart valve surgery, all patients receive an oral tablet of warfarin which is commenced two days post-surgery to protect them from forming blood clots on their new valve. Due to the nature of the action of warfarin and the need to stabilise each patient onto the best therapeutic dose specific to them, all patients routinely have a blood test called an INR (International Normalisation Ratio [INR] measurements) so as to monitor how thin their blood is and thus adjust the warfarin dose up or down so as to achieve and then maintain them within their target INR. While warfarin dosing is regulated to try to find the best therapeutic INR, subjects are routinely given an anticoagulant injection while the doctor adjusts the warfarin dose to get to a therapeutic INR and each patient on just the right dose of warfarin. We will compare two arms: - (Arm 1) The current warfarin dosing regimen (using the 'age-adjusted, warfarin management protocol' while in hospital and in Hospital-at-Home care, then empirical dosing once in GP care) over a 12 week period post mechanical heart valve surgery, - (Arm 2) Warfarin dosing post mechanical heart valve surgery following revised age-adjusted, warfarin management protocols, specifically designed to meet the needs of the post-mechanical aortic (therapeutic INR range of 2.0-2.5) and mitral (therapeutic INR range of 3.0-3.5) heart valve surgery patients. These investigational protocols, designed to cover the 12 week, post-surgery period, will include a specific first four day instruction for oral tablet warfarin dosing, where we will reduce the warfarin dosing of the currently used 'age-adjusted, warfarin management protocol' by 30% for patients receiving a mechanical aortic valve replacement so as to achieve an INR range of 2.0 to 2.5, and reduce the warfarin dosing by 25% for patients receiving a mechanical mitral valve replacement so as to achieve an INR of 3.0 to 3.5. Then from day 5, if the optimal anticoagulation status or therapeutic INR has reached a relative degree of steady-state or stability, we have added to the protocols the incremental dose adjustment approach described by Meijer et al (1), whereby dosing is adjusted up or down on a percentage basis depending on the INR. For patients not in the therapeutic INR range by day 5, empirical dosing will be recommended until INR steady state is achieved before the incremental dose adjustment approach as defined by Meijer et al (2), is applied. 1. Meijer K, Kim YK, Schulman S. Decreasing warfarin sensitivity during the first three months after heart valve surgery: Implications for dosing. Thromb Res. 2010 Mar;125(3):224-229. 2. Meijer K, Kim YK, Carter D, Schulman S. A prospective study of an aggressive warfarin dosing algorithm to reach and maintain INR 2 to 3 after heart valve surgery. Thromb Haemost. 2011 Feb;105(2):232-238. To monitor adherence a patient diary will be provided to all patients to collect INR results and warfarin dosing during the 12 week period. Also, INR results for all tests conducted during the 12 week period will be collected by the Principal Investigator. Dosage of oral warfarin will be analysed by intention to treat.