TY - JOUR
T1 - Determinants of the Quality of Warfarin Control after Venous Thromboembolism and Validation of the SAMe-TT2-R2 Score
T2 - An Analysis of Hokusai-VTE
AU - Barco, Stefano
AU - Granziera, Serena
AU - Coppens, Michiel
AU - Douxfils, Jonathan
AU - Nijkeuter, Mathilde
AU - Riva, Nicoletta
AU - Vanassche, Thomas
AU - Zhang, George
AU - Lin, Min
AU - Kamphuisen, Pieter W.
AU - Cohen, Alexander T.
AU - Beyer-Westendorf, Jan
N1 - Funding Information:
The Hokusai-VTE study was sponsored and funded by Daiichi Sankyo Pharma Development, Basking Ridge, New Jersey, United States. The authors are solely responsible for the content of this article. This study has been independently initiated by academic investigators; Daiichi Sankyo provided support for performing statistical analysis. The work of Stefano Barco is supported by the German Federal Ministry of Education (BMBF 01EO1003 and 01EO1503).
Publisher Copyright:
© 2019 Georg Thieme Verlag KG Stuttgart New York.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
KW - quality of treatment
KW - risk assessment model
KW - venous thromboembolism
KW - vitamin K antagonist
KW - warfarin
UR - http://www.scopus.com/inward/record.url?scp=85063205442&partnerID=8YFLogxK
U2 - 10.1055/s-0039-1678546
DO - 10.1055/s-0039-1678546
M3 - Article
C2 - 30731492
AN - SCOPUS:85063205442
SN - 0340-6245
VL - 119
SP - 675
EP - 684
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 4
ER -