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Direct oral anticoagulants and vitamin K antagonists are linked to differential profiles of cardiac function and lipid metabolism

  • Lisa Eggebrecht
  • Jürgen H. Prochaska
  • Sven-Oliver Tröbs
  • Sören Schwuchow-Thonke
  • Sebastian Göbel
  • Simon Diestelmeier
  • Andreas Schulz
  • Natalie Arnold
  • Marina Panova-Noeva
  • Thomas Koeck
  • Steffen Rapp
  • Tommaso Gori
  • Karl J. Lackner
  • Hugo ten Cate
  • Thomas Münzel
  • Philipp Sebastian WildEmail author
Original Paper
  • 134 Downloads

Abstract

Background

Experimental data indicate that direct acting oral anticoagulants (DOAC) and vitamin K antagonists (VKA) may exert differential effects on cardiovascular disease.

Methods

Data from the prospective, observational, single-center MyoVasc Study were used to examine associations of DOAC as compared to VKA with subclinical markers of cardiovascular disease, cardiac function, and humoral biomarkers in heart failure (HF).

Results

Multivariable analysis adjusted for age, sex, traditional cardiovascular risk factors, comorbidities, and medications with correction for multiple testing demonstrated that DOAC therapy was among all investigated parameters an independent significant predictor of better diastolic function (E/E′: β − 0.24 [− 0.36/− 0.12]; P < 0.0001) and higher levels of ApoA1 (β + 0.11 g/L [0.036/0.18]; P = 0.0038) compared to VKA therapy. In propensity score-weighted analyses, the most pronounced differences between DOAC and VKA-based therapy were also observed for E/E′ (∆ − 2.36) and ApoA1 (∆ + 0.06 g/L). Sensitivity analyses in more homogeneous subsamples of (i) individuals with AF and (ii) individuals with asymptomatic HF confirmed the consistency and robustness of these findings. In the comparison of factor IIa and Xa-directed oral anticoagulation, no differences were observed regarding cardiac function (E/E′ ratio: βIIa inhibitor − 0.22 [− 0.36/− 0.08] vs. βXa inhibitor − 0.24 [− 0.37/− 0.11]) and lipid metabolism (ApoA1: βIIa inhibitor 0.10 [0.01/0.18] vs. βXa inhibitor 0.12 [0.04/0.20]) compared to VKA therapy.

Conclusion

This study provides the first evidence for differential, non-conventional associations of oral anticoagulants on cardiac function and lipid metabolism in humans. The potentially beneficial effect of DOACs in the highly vulnerable population of HF individuals needs to be further elucidated and may have implications for individually tailored anticoagulation therapy.

Keywords

Anticoagulation Direct oral anticoagulants Vitamin K antagonist Cardiac function Lipids and lipid protein metabolism 

Notes

Acknowledgements

We gratefully thank all study participants and co-workers of the MyoVasc Study for their support and commitment. This work was supported by the German Center for Cardiovascular Research (DZHK) and the Center for Translational Vascular Biology (CTVB) of the University Medical Center of the Johannes Gutenberg-University Mainz. The sponsoring bodies played no role in the planning, conduct or analysis of the study.

Author contributions

PSW had full access of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Conception and study design: LE, JHP, and PSW. Substantial contribution to acquisition, analysis, or interpretation of data: all authors. Data management and statistical analysis: AS, LE, JHP, and PSW. Drafting the manuscript: LE, JHP, and PSW. Revising manuscript critically for important intellectual content: all authors. Final approval of the version to be published: all authors.

Compliance with ethical standards

Conflict of interest

P.S.W., M.P.N., and J.H.P. are funded by the Federal Ministry of Education and Research (BMBF 01EO1503). P.S.W. has received research funding from Boehringer Ingelheim; PHILIPS Medical Systems; Sanofi-Aventis; Bayer Vital; Daiichi Sankyo Europe; Federal Institute for Occupational Safety and Health (BAuA); Initiative ‘Health Economy’, Ministry of Health and Ministry of Economics, Rhineland-Palatinate; Federal Ministry of Education and Research; Federal Ministry of Health, Rhineland-Palatinate (MSAGD); Mainz Heart Foundation; EU Grant agreement no. 278913, 278397 and received honoraria for lectures or consulting from Boehringer Ingelheim, Bayer HealthCare, Evonik, AstraZenca and Sanofi-Aventis.

Supplementary material

392_2018_1408_MOESM1_ESM.docx (32 kb)
Supplementary material 1 (DOCX 31 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Lisa Eggebrecht
    • 1
    • 2
  • Jürgen H. Prochaska
    • 1
    • 2
    • 3
    • 4
  • Sven-Oliver Tröbs
    • 2
    • 3
    • 5
  • Sören Schwuchow-Thonke
    • 2
    • 3
    • 5
  • Sebastian Göbel
    • 2
    • 3
    • 5
  • Simon Diestelmeier
    • 2
    • 3
    • 5
  • Andreas Schulz
    • 1
    • 2
  • Natalie Arnold
    • 1
    • 2
  • Marina Panova-Noeva
    • 2
    • 3
    • 4
  • Thomas Koeck
    • 1
    • 3
  • Steffen Rapp
    • 1
    • 3
  • Tommaso Gori
    • 2
    • 3
    • 5
  • Karl J. Lackner
    • 3
    • 6
  • Hugo ten Cate
    • 4
    • 7
  • Thomas Münzel
    • 2
    • 3
    • 4
    • 5
  • Philipp Sebastian Wild
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Preventive Cardiology and Preventive Medicine, Center for CardiologyUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
  2. 2.Center for Translational Vascular Biology (CTVB)University Medical Center Mainz, Johannes Gutenberg-University MainzMainzGermany
  3. 3.German Center for Cardiovascular Research (DZHK), Partner Site Rhine MainMainzGermany
  4. 4.Center for Thrombosis and HemostasisUniversity Medical Center of the Johannes Gutenberg-University MainzMainzGermany
  5. 5.Center for Cardiology-Cardiology IUniversity Medical Center of the Johannes Gutenberg-University MainzMainzGermany
  6. 6.Institute of Clinical Chemistry and Laboratory MedicineUniversity Medical Center Mainz, Johannes Gutenberg-UniversityMainzGermany
  7. 7.Thrombosis Expertise Center MaastrichtCardiovascular Research Institute Maastricht, Maastricht University Medical CenterMaastrichtThe Netherlands

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