Pleotropic Effect of New Oral Anticoagulants

Study Overview
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Brief Summary
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Atrial fibrillation (AF) has been known to have several pathophysiologic mechanisms including endothelial dysfunction of heart and vessel. This study was designed to determine the efficacy of NOAC therapy in the prevention of endothelial dysfunction and progression of atherosclerosis of AF subjects.

Detailed Description
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The properties of oral, direct inhibitors of factor Xa (e.g. rivaroxaban) and thrombin (e.g. dabigatran) have been examined the haemostasis and thromboembolism management. Preclinical studies have provided evidences for the effects of direct factor Xa or thrombin inhibition beyond anticoagulation, including anti-inflammatory and protective activities in atherosclerotic plaque development . Therefore, this study evaluates the protective effects of NAOC with the reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements reflecting endothelial function by Endo-PAT2000 and intima-media thickness (IMT) of the carotid artery, which is used as a surrogate endpoint of atherosclerosis.

Official Title
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Prospective Randomized Study for Evaluating Vascular Protective Effects of New Oral Anticoagulants in High Risk Patients With Atrial Fibrillation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: dabigatran
* Drug: ribaroxaban
* Drug: Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CHA2DS2-VASc score above 2 Exclusion Criteria: severe peripheral arterial disease (greater than a Fontaine IIb category) grade 4 or higher cerebral infarction on the Modified Rankin Scale proven coronary artery disease by coronary angiogram severe hepatic or renal dysfunction uncontrolled congestive heart failure uncontrolled hypertension or diabetes mellitus hematologic disorders allergy or hypersensitivity to the investigational drugs pregnant or lactating women or women wishing to become pregnant

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dabigatran 110mg or 150mg<br>After once enrolled, subjects will be randomized to dabigatran group. (110mg or 150mg twice a day) | Drug: dabigatran<br>* After randomization, patients of this group was will be treated to dabigatran 110mg or 150mg twice a day for 24months<br>* Other names: pradaxa;|
| Experimental: ribaroxaban 20mg<br>After once enrolled, subjects will be randomized to ribaroxaban group. (20mg once daily) | Drug: ribaroxaban<br>* After randomization, patients of this group was will be treated to ribaroxaban 20mg once a day for 24months.<br>* Other names: xarelto;|
| Active Comparator: warfarin<br>After once enrolled, subjects will be randomized to warfarin group. (controlled by INR 2-3) | Drug: Warfarin<br>* After randomization, patients of this group was will be treated to warfarin and controlled by INR 2-3 for 24months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The changes in reactive hyperemia index (RHI) |  | 12months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| right and left maximum IMT of the common carotid artery (CCA) |  | 24months | 
| right and left mean IMT of the common carotid artery (CCA) |  | 24months | 
| adverse events |  | 24months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anticoagulant, atherosclerosis, endothelium