Defining time in therapeutic range for busy clinicians: frequency of dose changes is a good surrogate marker to identify patients with suboptimal anticoagulation with warfarin

Thromb Res. 2014 Sep;134(3):584-6. doi: 10.1016/j.thromres.2014.06.024. Epub 2014 Jul 6.

Abstract

Introduction: Patients on warfarin with sub-optimal time-in-therapeutic-range (TTR) are more likely to have adverse events. Target-specific oral anticoagulants (TSOACs) are approved and can be used as an alternative to warfarin for a number of indications. Further, the efficacy and safety profiles of the TSOACs compared to warfarin are more favourable when the TTR is ≤65% for certain indications.

Objective: We aimed to determine simple, sensitive and specific diagnostic tools to identify TTR ≤ 65% during the initial three months of warfarin therapy.

Methods: A cross-sectional study including patients newly initiated on warfarin without any interruption for three months was conducted. TTR was calculated using the Rosendaal method. Patients were stratified by TTR (≤ 65% or >65%). Number of INR measurements, dose changes and INR measurements of ≤ 1.7 or ≥ 4.0 were evaluated as potential diagnostic tools to identify TTR ≤ 65%.

Results: 670 patients were included. The most common indication for anticoagulation was venous thromboembolism. The mean TTR in the first three months was 68 ± 21% (Range: 10 to 100%). Three or more dose changes identified TTR ≤ 65% and demonstrated a sensitivity and specificity of 90% (95%CI 86 to 93%) and 56% (95%CI 51 to 61%), respectively. Three or more INR measurements of ≤ 1.7 during the initial three months of anticoagulation showed a sensitivity and specificity of 37% (95%CI 32 to 43%) and 98% (95%CI 96 to 99%), respectively.

Conclusion: Three or more dose changes and three or more INR measurements of ≤ 1.7 could identify patients with a TTR ≤ 65% in the first three months of warfarin therapy.

Keywords: Acenocoumarol; Venous thrombosis; Warfarin.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage*
  • Blood Coagulation / drug effects*
  • Cross-Sectional Studies
  • Drug Dosage Calculations*
  • Drug Monitoring / methods*
  • Female
  • Humans
  • International Normalized Ratio*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • Venous Thromboembolism / blood
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / drug therapy*
  • Warfarin / administration & dosage*
  • Young Adult

Substances

  • Anticoagulants
  • Warfarin