Determinants of the Quality of Warfarin Control after Venous Thromboembolism and Validation of the SAMe-TT2-R2 Score: An Analysis of Hokusai-VTE

Stefano Barco, Serena Granziera, Michiel Coppens, Jonathan Douxfils, Mathilde Nijkeuter, Nicoletta Riva, Thomas Vanassche, George Zhang, Min Lin, Pieter W Kamphuisen, Alexander T Cohen, Jan Beyer-Westendorf

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BACKGROUND:  Time in therapeutic range (TTR) measures the quality of vitamin K antagonist (VKA) anticoagulation. In patients with atrial fibrillation, the dichotomized SAMe-TT2-R2 score (≥2 vs. < 2 points) can predict if adequate TTR is unlikely to be achieved.

AIMS:  We validated the SAMe-TT2-R2 score in patients with venous thromboembolism (VTE) randomized to the warfarin arm of the Hokusai-VTE trial.

PATIENTS AND METHODS:  A total of 3,874 patients were included in the primary analysis (day 31-180 from randomization). The efficacy and safety outcomes were symptomatic recurrent VTE and major or clinically relevant non-major bleeding.

RESULTS:  The rates of recurrent VTE and bleeding events were higher in patients with a TTR below the median (< 66% vs. ≥66%) resulting in an absolute risk difference (ARD) of +0.5% (95% confidence interval: 0%, +1.1%) and +2.2% (0.9%, +3.5%), respectively. Patients with high SAMe-TT2-R2 score were 76% of total and had lower median TTR (64.7% vs. 70.7%). The SAMe-TT2-R2 score exhibited low negative (0.59) and positive (0.52) predictive value (TTR threshold 66%), and poor discrimination (c-statistic, 0.58). ARD between patients with high and low score was 0% (-0.6%, +0.7%) for recurrence and +1.3% (-0.1%, +2.7%) for bleeding. Results were confirmed in sensitivity analyses focusing on the whole study period (day 1-365).

CONCLUSION:  In VTE patients, the SAMe-TT2-R2 score showed unsatisfactory discrimination and predictive value for individual TTR and did not correlate well with clinical outcomes. The choice of starting a patient on VKA cannot be based on this parameter and its routine use after VTE may not translate into clinical usefulness.

Original languageEnglish
Pages (from-to)675-684
Number of pages10
JournalThrombosis and haemostasis
Issue number4
Publication statusPublished - Apr 2019


  • Adult
  • Anticoagulants/therapeutic use
  • Atrial Fibrillation/blood
  • Blood Coagulation/drug effects
  • Double-Blind Method
  • Female
  • Hemorrhage/drug therapy
  • Humans
  • International Normalized Ratio
  • Linear Models
  • Male
  • Middle Aged
  • Recurrence
  • Research Design
  • Risk Assessment
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome
  • Venous Thromboembolism/drug therapy
  • Vitamin K/antagonists & inhibitors
  • Warfarin/therapeutic use

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