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Thromb Haemost 2015; 114(06): 1136-1143
DOI: 10.1160/TH14-12-1033
Coagulation and Fibrinolysis
Schattauer GmbH

Independent predictors of poor vitamin K antagonist control in venous thromboembolism patients

Data from the EINSTEIN-DVT and PE studies
Hilde A. M. Kooistra
1   Division of Haemostasis and Thrombosis, Department of Haematology, University of Groningen, University Medical Centre Groningen, The Netherlands
,
Martin Gebel
2   Bayer HealthCare, Wuppertal, Germany
,
Kurtulus Sahin
3   ClinStat GmbH, Cologne, Germany
,
Anthonie W. A. Lensing
2   Bayer HealthCare, Wuppertal, Germany
,
Karina Meijer
1   Division of Haemostasis and Thrombosis, Department of Haematology, University of Groningen, University Medical Centre Groningen, The Netherlands
› Author Affiliations
Further Information

Publication History

Received: 12 December 2014

Accepted after major revision: 26 June 2015

Publication Date:
30 November 2017 (online)

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Summary

Vitamin K antagonists (VKA) are used to prevent recurrent disease in patients with venous thromboembolism (VTE). Their efficacy and safety depend on individual time in therapeutic range (iTTR) and variability of International Normalised Ratios (INR). We aimed to identify independent predictors of poor VKA control > 28 days. In a prospective cohort of 3825 VTE patients, separate logistic regression analyses were performed to identify predictors of low iTTR (first quartile) and instability (iTTR <median and variability >median). Subsequently, the association between these predictors and clinical outcomes was investigated. Weight < 50 kg (odds ratio [OR]=1.89; 95 % confidence interval [CI] 1.03–3.49), active cancer at baseline (OR=1.52; CI1.05–2.19), secondary VTE (OR=1.42; CI1.20–1.68), and INR < 2.0 at stop of double therapy (OR=1.35; CI1.09–1.67) were independent predictors of low iTTR. The first two were also predictive for instability (OR=1.96; CI1.06–3.63 and OR=1.95; CI1.36–2.80, respectively). ORs of early ( 28 days) low iTTR and instability depended on VKA type. In acenocoumarol users, early low iTTR was an independent predictor of subsequent low iTTR (OR=1.92; CI1.31–2.80) and instability (OR=1.55; CI1.07–2.23). In warfarin users, early low iTTR (OR=1.36; CI1.09–1.69) and instability (OR=1.25; CI1.01–1.55) were additionally predictive for low iTTR, but only the latter was predictive for instability (OR=1.91; CI1.57–2.32). Many predictors of VKA control also predicted premature discontinuation, but only region was prognostic for clinical outcome. In conclusion, we identified several independent predictors of low iTTR and instability > 28 days, which showed some similarities but did not fully overlap. Early VKA control was of additional value for prediction of both, but had to be interpreted in the context of VKA type.

Keywords

Venous thrombosis - vitamin K antagonists - predictors - iTTR - instability
 

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