Cognitive Impairment Related to Atrial Fibrillation Prevention Trial

Study Overview
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Brief Summary
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Cognitive and functional decline observed in atrial fibrillation (AF) patients are related to thrombotic and/or cardioembolic events. Use of warfarin for the prevention of stroke in AF patients, despite effective, remains beyond desired levels because of interactions with food and fluctuations in blood levels. Because of a more stable anticoagulation state, Dabigatran may offer better protection against thrombotic phenomenon and, consequently, mitigate the process of cognitive and functional compromise.

Detailed Description
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This will be a prospective parallel study including two hundred atrial fibrillation patients > 65 years old and scoring CHADS2VASc > 1. Patients will be randomized to receive Warfarin (INR between 2 and 3) or Dabigatran (150 mg twice daily) for two years. After one year and at the end of the study, individuals will be evaluated regarding cognitive endpoints following the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards (Hachinski et al. Stroke 2006;37:2220-2241). The investigators will use the 60 minutes evaluation protocol complemented by the Montreal Cognitive Assessment (MoCA).

Official Title
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Randomized Clinical Trial for the Prevention of Cognitive Impairment in Atrial Fibrillation Patients Treated With Dabigatran or Warfarin

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: Warfarin
* Drug: Dabigatran


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Atrial fibrillation CHA2DS2-VASc Score for Atrial Fibrillation Stroke Risk (CHADS2VASc) greater than 1 Exclusion Criteria: Heart valve disease Previous Stroke or Transient ischemic attack Cognitive impairment or any severe neurological disorder Major surgery in the last 30 days Planned elective surgery in the next three months Intracranial, ocular, spinal, retroperitoneal, or articular bleeding without trauma. Gastrointestinal bleeding in the last 12 months Symptomatic gastric ulcer Hemorrhagic disease Use of thrombolytics Uncontrolled hypertension Active cancer Contraindication for Warfarin use Reversible causes of atrial fibrillation Creatinine clearance < 30 ml/min Active endocarditis Active hepatitis Severe anemia Left ventricle ejection fraction < 35%

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Warfarin<br>Treatment with Warfarin once daily, taken at fast, to maintain INR between 2 and 3. | Drug: Warfarin<br>* Warfarin once daily, at fast, targeting INR between 2 and 3<br>* Other names: Marevan, Coumadin;|
| Active Comparator: Dabigatran<br>Dabigatran 150 mg twice daily | Drug: Dabigatran<br> <br> * Other names: Dabigatran 150 mg twice daily;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive impairment | Cognitive impairment at two years, independently of stroke or other cerebrovascular events. | Two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with less important alteration in coagulation test as a Measure of Safety | Comparison of thrombin generation test between the two treatment groups. | Two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial fibrillation, Cognition, Cognitive impairment, Anticoagulation, Dabigatran, Warfarin, Efficacy