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

J Thromb Haemost. 2014 Aug;12(8):1254-9. doi: 10.1111/jth.12613. Epub 2014 Jun 25.


Background: There is uncertainty regarding the optimal dosing regimen for the resumption of warfarin after interruption for invasive procedures.

Aim: To determine the efficacy and safety of warfarin resumption with loading doses or with the most recent maintenance dose.

Methods: 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.

Results: 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.

Conclusion: Resumption of warfarin after minor-moderately invasive procedures with two loading doses achieves therapeutic INR faster than does only maintenance dose.

Trial registration: ClinicalTrials.gov NCT01348074.

Keywords: D-dimer; anticoagulation; bleeding; international normalized ratio; surgery.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anticoagulants / administration & dosage*
  • Female
  • Fibrin Fibrinogen Degradation Products
  • Humans
  • International Normalized Ratio
  • Male
  • Prospective Studies
  • Surgical Procedures, Operative*
  • Warfarin / administration & dosage*


  • Anticoagulants
  • Fibrin Fibrinogen Degradation Products
  • fibrin fragment D
  • Warfarin

Associated data

  • ClinicalTrials.gov/NCT01348074