Loading dose vs. maintenance dose of warfarin for reinitiation after invasive procedures: a randomized trial

Abstract

There is uncertainty regarding the optimal dosing regimen for the resumption of warfarin after interruption for invasive procedures. To determine the efficacy and safety of warfarin resumption with loading doses or with the most recent maintenance dose. Patients receiving warfarin treatment and planned for invasive procedures with an expected hospital stay of ≤ 1 day were randomized to resume warfarin on the day of the procedure, defined as day 1, with most recent maintenance dose or with 2 initial days of double maintenance dose. Efficacy outcomes were proportion of international normalized ratio (INR) levels ≥ 2.0 on day 5 (primary outcome) and day 10. Safety outcomes were bleeding and thromboembolic events. In addition, D-dimer levels were analyzed on days 5 and 10 in a subset of the population. There were 49 patients analyzed in each group. INR of ≥ 2.0 had been achieved by day 5 for 13% in the maintenance-dose group and for 50% in the loading-dose group (relative risk [RR] 0.27, 95% confidence interval [CI] 0.10-0.60) and by day 10 for 68% and 87%, respectively (RR 0.78, 95% CI 0.65-1.00). There were no thromboembolic events, and there was one major bleed before resumption of warfarin and one minor bleed, both in the maintenance-dose group. There was no difference between the groups in the proportion of patients with excessive INRs or elevated D-dimer levels or in the median D-dimer level. Resumption of warfarin after minor-moderately invasive procedures with two loading doses achieves therapeutic INR faster than does only maintenance dose.