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

doi:10.1055/s-0039-1678546

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

^*Corresponding author for this work

Cardiovascular Centre (CVC)

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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 language	English
Pages (from-to)	675-684
Number of pages	10
Journal	Thrombosis and Haemostasis
Volume	119
Issue number	4
DOIs	https://doi.org/10.1055/s-0039-1678546
Publication status	Published - Apr-2019

Keywords

vitamin K antagonist
quality of treatment
warfarin
venous thromboembolism
risk assessment model
NONVALVULAR ATRIAL-FIBRILLATION
VITAMIN-K ANTAGONISTS
ANTICOAGULATION CONTROL
EXTERNAL VALIDATION
ORAL ANTICOAGULANT
THERAPY
RISK
TIME
EDOXABAN
PREDICTS

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Determinants of the Quality of Warfarin Control after Venous Thromboembolism and Validation of the SAMe-TT2-R2 ScoreFinal publisher's version, 256 KBLicence: Taverne

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Barco, S., Granziera, S., Coppens, M., Douxfils, J., Nijkeuter, M., Riva, N., Vanassche, T., Zhang, G., Lin, M., Kamphuisen, P. W., Cohen, A. T., & Beyer-Westendorf, J. (2019). Determinants of the Quality of Warfarin Control after Venous Thromboembolism and Validation of the SAMe-TT2-R2 Score: An Analysis of Hokusai-VTE. Thrombosis and Haemostasis, 119(4), 675-684. https://doi.org/10.1055/s-0039-1678546

@article{130beaed7694474a900475243ad78f8a,

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

abstract = "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.",

keywords = "vitamin K antagonist, quality of treatment, warfarin, venous thromboembolism, risk assessment model, NONVALVULAR ATRIAL-FIBRILLATION, VITAMIN-K ANTAGONISTS, ANTICOAGULATION CONTROL, EXTERNAL VALIDATION, ORAL ANTICOAGULANT, THERAPY, RISK, TIME, EDOXABAN, PREDICTS",

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

year = "2019",

month = apr,

doi = "10.1055/s-0039-1678546",

language = "English",

volume = "119",

pages = "675--684",

journal = "Thrombosis and Haemostasis",

issn = "0340-6245",

publisher = "GEORG THIEME VERLAG KG",

number = "4",

}

Barco, S, Granziera, S, Coppens, M, Douxfils, J, Nijkeuter, M, Riva, N, Vanassche, T, Zhang, G, Lin, M, Kamphuisen, PW, Cohen, AT & Beyer-Westendorf, J 2019, 'Determinants of the Quality of Warfarin Control after Venous Thromboembolism and Validation of the SAMe-TT2-R2 Score: An Analysis of Hokusai-VTE', Thrombosis and Haemostasis, vol. 119, no. 4, pp. 675-684. https://doi.org/10.1055/s-0039-1678546

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

PY - 2019/4

Y1 - 2019/4

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 - vitamin K antagonist

KW - quality of treatment

KW - warfarin

KW - venous thromboembolism

KW - risk assessment model

KW - NONVALVULAR ATRIAL-FIBRILLATION

KW - VITAMIN-K ANTAGONISTS

KW - ANTICOAGULATION CONTROL

KW - EXTERNAL VALIDATION

KW - ORAL ANTICOAGULANT

KW - THERAPY

KW - RISK

KW - TIME

KW - EDOXABAN

KW - PREDICTS

U2 - 10.1055/s-0039-1678546

DO - 10.1055/s-0039-1678546

M3 - Article

SN - 0340-6245

VL - 119

SP - 675

EP - 684

JO - Thrombosis and Haemostasis

JF - Thrombosis and Haemostasis

IS - 4

ER -

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

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