Direct oral anticoagulants and vitamin K antagonists are linked to differential profiles of cardiac function and lipid metabolism
- 138 Downloads
Experimental data indicate that direct acting oral anticoagulants (DOAC) and vitamin K antagonists (VKA) may exert differential effects on cardiovascular disease.
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).
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.
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.
KeywordsAnticoagulation Direct oral anticoagulants Vitamin K antagonist Cardiac function Lipids and lipid protein metabolism
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.
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.
- 9.Kadoglou NP, Moustardas P, Katsimpoulas M et al (2012) The beneficial effects of a direct thrombin inhibitor, dabigatran etexilate, on the development and stability of atherosclerotic lesions in apolipoprotein E-deficient mice: dabigatran etexilate and atherosclerosis. Cardiovasc Drugs Ther 26(5):367–374CrossRefGoogle Scholar
- 19.Yoshimura F, Tanikawa S, Hosako S, Kato R (2015) Factor Xa inhibition prevents cardiac remodeling induced by intermittent hypoxia in sleep apnea model mice. Circulation 132:A13846Google Scholar
- 38.Bodde MC, Hermans MPJ, Jukema JW et al (2018) Apolipoproteins A1, B, and apoB/apoA1 ratio are associated with first ST-segment elevation myocardial infarction but not with recurrent events during long-term follow-up. Clin Res Cardiol. https://doi.org/10.1007/s00392-018-1381-5 CrossRefPubMedGoogle Scholar