A randomized trial of restarting warfarin at maintenance versus loading doses following an elective procedure

Guidelines suggest restarting warfarin at known maintenance doses, although this may result in a delay to achieving therapeutic anticoagulation. As such, we compared the time to achieve an INR ≥ 2.0 between those restarting warfarin maintenance vs loading doses after transient interruption, and the impact on protein C, S and factor II levels. Patients requiring interruption of warfarin for elective procedures without hospitalization were randomized 1:1 to receive warfarin maintenance or loading doses (1.5 times the maintenance dose for 3 days followed by pre-procedural warfarin maintenance dosing). Protein C, S and Factor II were drawn at baseline (prior to warfarin interruption), 7 and 14 days after restarting warfarin. Among 19 patients randomized to maintenance and 20 to loading doses, nearly half in each group had mechanical heart valves with gastrointestinal endoscopic procedures most commonly performed (41%). The median number of days to reach an INR ≥ 2.0 was 7.8 days in the loading and 9.0 in the maintenance group (difference between medians 1.2 days, 95% CI -3.1 to 4.9; P = 0.19). Although levels of protein C, S and factor II were lower in the loading vs maintenance dose group, all remained above that of baseline. Warfarin resumption with loading doses shortened the time to achieve a therapeutic INR by a median of 1.2 days. Prompt warfarin dose escalation should be done in response to the INR. Protein C and S remained above pre-warfarin interruption levels, implying a lack of depletion with restarting warfarin.