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

Abstract

IntroductionPatients 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. ObjectiveWe aimed to determine simple, sensitive and specific diagnostic tools to identify TTR≤65% during the initial three months of warfarin therapy. MethodsA 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%. Results670 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. ConclusionThree 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.