Evaluation of the vascular protective effects of new oral anticoagulants in high-risk patients with atrial fibrillation (PREFER-AF): study protocol for a randomized controlled trial.

Jin-Bae Kim,Kyung Hye Lee,Kwon Sam Kim,Weon Kim,Hyun Jun Joung,Jong Shin Woo,Jung Myung Lee,Woo-Shik Kim

doi:10.1186/s13063-016-1541-8

Abstract

BackgroundAtrial fibrillation (AF) is known to be associated with several pathophysiological mechanisms including endothelial dysfunction of the heart and arterial vessels. Recent evidence suggests that new oral anticoagulant (NOAC) treatment may improve endothelial function and the inflammatory process involved in atherosclerosis in AF patients. This study is designed to determine the efficacy of NOAC therapy in the prevention of endothelial dysfunction and the progression of atherosclerosis of AF subjects.Method/designAF patients with a CHA2DS2-VASc score >2 and no previous history of overt coronary disease, severe peripheral arterial disease (PAD) or major stroke will be registered and randomly assigned either to the NOAC group (dabigatran or rivaroxaban) or the warfarin group in this prospective, randomized, 2-year follow-up study. Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements reflecting endothelial function will be conducted using the Endo-PAT2000 device. Left and right carotid intima-media thickness (IMT) will be measured at baseline, 12 months, and 24 months. The primary endpoint is defined as change in Reactive Hyperemia Index (RHI) at 12 months. Secondary endpoints included changes in the right and left maximum IMT of the common carotid artery (CCA) and internal carotid artery (ICA), the mean IMT of the CCA and ICA at 24 months, and 24-month cardiovascular events including cardiac death, stroke, acute myocardial infarction (AMI), overall cause of death, withdrawal of drug, or bleeding events.DiscussionThis is the first study to evaluate the efficacy of NOAC therapy for the prevention of endothelial dysfunction and progression of atherosclerosis in AF subjects. These findings are expected to expand the knowledge of NOAC pleotropic action in AF patients.Trial registrationClinicalTrials.gov: NCT02544932, registered on 7 September 2015.

Highlights

Atrial fibrillation (AF) is known to be associated with several pathophysiological mechanisms including endothelial dysfunction of the heart and arterial vessels
This is the first study to evaluate the efficacy of new oral anticoagulant (NOAC) therapy for the prevention of endothelial dysfunction and progression of atherosclerosis in AF subjects
These findings are expected to expand the knowledge of NOAC pleotropic action in AF patients

Summary

Introduction

Atrial fibrillation (AF) is known to be associated with several pathophysiological mechanisms including endothelial dysfunction of the heart and arterial vessels. Cross-talk between coagulation and inflammatory pathways via thrombin- or factor Xa-mediated PAR activation on the arterial vessel wall and heart, and the resulting contribution to atherosclerosis and atrial fibrillation (AF), have been well-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 [5,6,7,8]. Evidence has demonstrated that direct thrombin inhibition impairs the formation and size of atherosclerotic plaques in addition to preventing the progression of endothelial injury-associated stenosis in an apolipoprotein E-deficient mouse model [5, 6]. Factor Xa inhibition was shown to ensure the reduction of restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits [7]

Objectives

Methods

Findings

Conclusion