Thromb Haemost
DOI: 10.1055/s-0039-1692175
Stroke, Systemic or Venous Thromboembolism
Georg Thieme Verlag KG Stuttgart · New York

Subtherapeutic Anticoagulation Control under Treatment with Vitamin K-Antagonists—Data from a Specialized Coagulation Service

Jürgen H. Prochaska
1  Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany
2  Center for Thrombosis and Hemostasis, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany
3  German Center for Cardiovascular Research (DZHK), Partner Site RhineMain, Mainz, Germany
,
Christoph Hausner
1  Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany
,
Markus Nagler
1  Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany
2  Center for Thrombosis and Hemostasis, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany
,
Sebastian Göbel
4  Center for Cardiology–Cardiology I, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany
3  German Center for Cardiovascular Research (DZHK), Partner Site RhineMain, Mainz, Germany
,
Lisa Eggebrecht
1  Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany
,
Marina Panova-Noeva
1  Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany
2  Center for Thrombosis and Hemostasis, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany
3  German Center for Cardiovascular Research (DZHK), Partner Site RhineMain, Mainz, Germany
,
Natalie Arnold
1  Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany
,
Michael Lauterbach
5  Department of Medicine 3, Barmherzige Brüder Hospital Trier, Trier, Germany
,
Christoph Bickel
6  Department of Medicine I, Federal Armed Forces Central Hospital, Koblenz, Germany
,
Matthias Michal
7  Department of Psychosomatic Medicine and Psychotherapy, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany
,
Roland Hardt
8  Center for General Medicine and Geriatrics, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany
,
Christine Espinola-Klein
4  Center for Cardiology–Cardiology I, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany
,
Karl J. Lackner
9  Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany
3  German Center for Cardiovascular Research (DZHK), Partner Site RhineMain, Mainz, Germany
,
Thomas Münzel
4  Center for Cardiology–Cardiology I, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany
3  German Center for Cardiovascular Research (DZHK), Partner Site RhineMain, Mainz, Germany
2  Center for Thrombosis and Hemostasis, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany
,
Philipp S. Wild
1  Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany
2  Center for Thrombosis and Hemostasis, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany
3  German Center for Cardiovascular Research (DZHK), Partner Site RhineMain, Mainz, Germany
› Author Affiliations
Funding This work was supported by grants of the state initiative “health economy” of the Ministries of Health and Economics, Rhineland-Palatinate, Germany (grant identifier: AZ.623-1), the Federal Ministry of Education and Research, Germany (grant identifier: BMBF 10E01003), the Center for Translational Vascular Biology (CTVB) of the University Medical Center Mainz, Boehringer Ingelheim Pharma GmbH & Co. KG, Bayer Vital GmbH, Daiichi Sankyo Europe GmbH, Sanofi-Aventis Germany GmbH, IMO Institute GmbH, Portavita BV, and the German Heart Foundation. Dr. ten Cate is a fellow of the Gutenberg Forschungskolleg of the Johannes Gutenberg University, Mainz, Germany. Drs. Prochaska, Panova-Noeva, and Wild are funded by the German Federal Ministry of Education and Research (grant identifier: BMBF 10E01003). The sponsoring bodies played no role in the planning, conduct, or analysis of the study.
Further Information

Publication History

13 November 2019

11 April 2019

Publication Date:
10 June 2019 (eFirst)

Abstract

In contrast to overanticoagulation, evidence on risk factors and outcome of subtherapeutic oral anticoagulation (OAC) with vitamin K-antagonists (VKAs) under optimum care is limited. We investigated the clinical phenotype, anticoagulation control, and clinical outcome of 760 VKA patients who received OAC therapy by a specialized coagulation service in the thrombEVAL study (NCT01809015). During 281,934 treatment days, 278 patients experience ≥ 1 episode of subtherapeutic anticoagulation control and had lower quality of OAC therapy compared to 482 patients without subtherapeutic international normalized ratio: 67.6%, interquartile range (IQR) 54.9%/76.8% versus 81.0%, IQR 68.5%/90.4%; p < 0.001. In Cox regression analysis with adjustment for age, sex, cardiovascular risk factors, comorbidities, and treatment characteristics, female sex (hazard ratio [HR], 1.4, 95% confidence interval [CI], 1.0/1.9; p = 0.03), diabetes (HR, 1.4, 95% CI, 1.0/2.0; p = 0.03), and living alone (HR, 1.5, 95% CI, 1.1/2.1; p = 0.009) were independent risk factors of subtherapeutic anticoagulation control, whereas atrial fibrillation (HR, 0.6, 95% CI, 0.4/0.9; p = 0.02) and self-management of OAC therapy (HR, 0.2, 95% CI, 0.1/0.6; p = 0.001) were protective. In addition, active smoking (HR, 1.7, 95% CI, 0.9/3.0; p = 0.086) and living in a nursing home (HR, 1.6, 95% CI, 0.8/3.2; p = 0.15) indicated an elevated risk at the borderline of statistical significance. For the prediction of recurrent subtherapeutic anticoagulation, living alone was the only independent risk factor (HR, 1.7, 95% CI, 1.1/2.5; p = 0.013). The present study suggests that women, diabetics, and patients living alone experience an increased risk of low-quality VKA therapy and might potentially benefit from treatment with direct-acting anticoagulants.

Authors' Contributions

All authors contributed to conception and design of the study. J.H.P., C.H., M.N., and P.S.W. designed and conducted the statistical analysis. J.H.P., S.G., C.E., T.M., and P.S.W. contributed to data collection. J.H.P., S.G., and M.N. performed data management and quality control. J.H.P. and P.S.W. drafted the manuscript, which was critically revised for important intellectual content by all authors. All authors had access to the complete data set, contributed to the interpretation of data, and approved the final version of the manuscript. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.


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