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.
KeywordsPeriprocedural management Protein C Protein S Warfarin
Peer reviewed funding was received through the University Hospital Foundation Medical Research Competition, Office of Research, Faculty of Medicine and Dentistry, University of Alberta. Pfizer, Canada supplied dalteparin (Fragmin™) prefilled syringes for use in this research study. The sponsors had no role in the conduct of this research, the collection, analysis and interpretation of data; in writing the report nor the decision to submit the article for publication.
Compliance with ethical standards
Conflict of interest
TJB has received honoraria for an advisory board for BMS-Pfizer and Boehringer Ingelheim, as well as honoraria for speaking from Bayer. TJB has received unrestricted grants from BMS Pfizer and Bayer. JM has nothing to disclose. BR has served on advisory boards, given sponsored lectures using his own slides and received travel expense remuneration for Bayer, Baxter, Beohringer-Ingelheim, CSL-Behring, Pfizer, Sanofi, Servier and Shire. In lieu of honoraria for these activities, the companies have given financial contributions to the University of Alberta. BR reports grants from Novo Nordisk, CSL-Behring and Baxter, all outside of this submitted work.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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