Post-operative Warfarin re-initiation - modelling a loading dose strategy

Background: Guidelines recommend re-initiating postoperative warfarin at the previous maintenance dose. This results in prolonged re-establishment of a therapeutic international normalised ratio (INR). Modelling warfarin initiation and subsequent INR response using previously published data indicated that re-initiation with twice the maintenance dose for 3 days may provide a rapid alternative. Aim: To compare the time to a stable therapeutic INR for conventional maintenance dose re-initiation of warfarin with a loading dose strategy. Method: Warfarin maintenance doses were adjusted by using the standardised maintenance dose - a theoretical dose resulting in an INR of 2.5. The test group was re-initiated on warfarin doses twice their standardised maintenance dose on Days 1, 2 and 3 and on Day 4 reverted to their maintenance dose. The guideline group was re-initiated on warfarin doses equivalent to their standardised maintenance dose on these days. Results: The test group (n = 17) achieved a therapeutic INR more rapidly than the guideline group (n = 23; p < 0.001) with median times to therapeutic INR of 3 and 6 days respectively. After 3 doses the test group INR on Day 4 was in the therapeutic range (2.1±0.4) and signifi cantly higher than the guideline group (1.7±0.5; p = 0.002). No patient in the test group experienced an elevated INR (maximum INR 3.3). Conclusion: INR response to the warfarin re-initiation dose was dependent on the magnitude of the induction dose relative to the maintenance dose. The loading dose strategy achieved a stable therapeutic INR more rapidly than conventional practice. Prospective investigation in surgical patients is needed to confi rm its clinical applicability.