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

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: β_{IIa inhibitor} - 0.22 [- 0.36/- 0.08] vs. β_{Xa inhibitor} - 0.24 [- 0.37/- 0.11]) and lipid metabolism (ApoA1: β_{IIa inhibitor} 0.10 [0.01/0.18] vs. β_{Xa 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; Cardiac function; Direct oral anticoagulants; Lipids and lipid protein metabolism; Vitamin K antagonist.