Vascular Protective Effects of New Oral Anticoagulants in Patients with Atrial Fibrillation.

Gyeong-Won Jang,Weon Kim,Hyemoon Chung,Seung Woo Choi,Jong Shin Woo,Jung Myung Lee,Hyung Oh Kim,Jin Bae Kim,Joan Kim,Woo-Shik Kim,Young Shin Lee

doi:10.3390/jcm10194332

Abstract

This study was designed to determine the efficacy of a new oral anticoagulant (NOAC) therapy for the prevention of endothelial dysfunction and atherosclerosis progression in patients with atrial fibrillation (AF). Sixty-five AF patients with a CHA2DS2-VASc score ≥2 without previous history of cardiovascular disease were registered and randomly assigned to either an NOAC group (dabigatran or rivaroxaban) or the warfarin group. Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements reflecting endothelial function were taken using Endo-PAT2000. Carotid intima–media thickness (IMT) was measured at baseline, 12 months, and 24 months, and several biomarkers were also analyzed. For the primary end point, the reactive hyperemia index (RHI) for the NOAC group was 1.5 ± 0.4 and that for the warfarin group was 1.6 ± 0.5. The left and right carotid IMT was 0.7 mm in the NOAC groups and 0.8 mm in the warfarin group. At 12 months, RHI was 1.6 ± 0.3 for the dabigatran group, 1.6 ± 0.5 for the rivaroxaban group, and 1.6 ± 0.3 for the warfarin group. The three groups did not differ statistically with respect to change in left and right carotid IMT at 12 and 24 months, respectively. The biomarkers for endothelial function and atherosclerosis were not significantly different. There was a trend of reduced P-selectin levels in the NOAC group compared to the warfarin group. In patients with AF, there were no significant differences in the prevention of endothelial dysfunction and atherosclerosis progression between the NOAC and warfarin groups.

Highlights

Activated coagulation factor Xa is known to play a central role in the coagulation cascade
This study aimed to determine the efficacy of new oral anticoagulant (NOAC) therapy for preventing endothelial dysfunction and atherosclerosis progression in atrial fibrillation (AF) patients
There were no significant differences in patient characteristics between the three groups

Summary

Introduction

Activated coagulation factor Xa is known to play a central role in the coagulation cascade. Recent evidence further suggests that factor Xa has an important modulating effect in cellular signaling by the activation of protease-activated receptor (PAR) [1]. PAR activation on the arterial vessel wall and heart, and the resulting development of atherosclerosis and atrial fibrillation (AF) has been documented [2]. Preclinical studies have provided evidence for the effects of direct Xa or thrombin inhibition beyond anticoagulation, including anti-inflammatory and protective activities in atherosclerotic plaque development [1]. Evidence has demonstrated that direct thrombin inhibition impairs the formation and size of atherosclerotic plaques in addition to preventing progression of endothelial injury-associated stenosis in an apolipoprotein E-deficient mouse model [3,4]. The question remains as to whether these effects obtained in preclinical trials are similar in humans, for which there is scant evidence

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