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

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.

Informations de copyright

Georg Thieme Verlag KG Stuttgart · New York.

Déclaration de conflit d'intérêts

Stefano Barco has received congress and travel payments from Bayer HealthCare and Daiichi-Sankyo, lecture honoraria from BTG Interventional Medicine and financial support for the printing costs of his PhD thesis from Pfizer BV, CSL Behring bv, Sanquin Plasma Products, Boehringer Ingelheim bv, Aspen Netherlands and Bayer bv. Serena Granziera has received congress and travel payments from Daiichi-Sankyo, Bayer and Boehringer Ingelheim. Michiel Coppens reports grants from Boehringer Ingelheim, grants, personal fees, non-financial support and other from Bayer, grants, personal fees, non-financial support and other from Daiichi Sankyo, other from Pfizer, personal fees from Bristol Myers Squibb, other from Portola, personal fees and non-financial support from CSL Behring, personal fees from Aspen Pharma Group. J. Douxfils is CEO and founder of QUALIblood s.a. and reports personal fees from Stago and Daiichi-Sankyo. Mathilde Nijkeuter and Nicoletta Riva have no relevant disclosures. Thomas Vanassche has received speaker's fee and/or participated in advisory boards from Boehringer Ingelheim, Pfizer, Daiichi Sankyo and Bayer. George Zhang and Min Lin are employees of Daiichi-Sankyo Inc. Pieter W. Kamphuisen has received honoraria from LEO Pharma. Alexander Cohen reports grants and personal fees from BristolMyers Squibb and Pfizer Limited and personal fees from Boehringer Ingelheim, Johnson & Johnson, Portola, Sanofi Aventis, XO1, Janssen, Bayer HealthCare and grants from Daiichi Sankyo. Jan Beyer-Westendorf reports grants and personal fees from Bayer AG, Boehringer-Ingelheim, Daiichi Sankyo, Pfizer and Portola