Trial of Apixaban vs Warfarin in Reducing Rate of Cognitive Decline, Silent Cerebral Infarcts and Cerebral Microbleeds in Patients With Atrial Fibrillation

Study Overview
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Brief Summary
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The investigators' central hypothesis is that in patients with atrial fibrillation, anticoagulation with Apixaban reduces the rate of decline in cognitive function, when compared to Warfarin. The investigators also hypothesize that Apixaban reduces cognitive decline by reducing the rate of new cerebral infarction and cerebral microbleeds detected by cerebral MRI compared to warfarin.

Official Title
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Randomized Trial of Apixaban vs Dose Adjusted Warfarin in Reducing Rate of Cognitive Function Decline, Silent Cerebral Infarcts and Cerebral Microbleeds in Non-valvular Atrial Fibrillation Patients With CHA2DS2-VaSc Score = 2

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: Apixaban
* Drug: Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-valvular Atrial Fibrillation CHA2DS2-VASc Score > or = to 2 Never been treated with Apixaban (Eliquis) or prior treatment of < 1 month Candidate for oral anticoagulation as assessed by a treating physician Exclusion Criteria: Valvular Atrial Fibrillation (Rheumatic valve disease,Moderate or greater mitral stenosis,Mechanical cardiac valve) Active Bleeding Prior treatment with Apixaban >1 month Recent stroke within 7 days Dementia Implanted devices not compatible with MRI/any cardiac implanted device Claustrophobia Active alcohol/drug abuse Life expectancy < 1 year Taking asprin with >100mg doses Known hypersensitivity to warfarin or Apixaban Severe renal insufficiency Prior severe bleeding (Intracranial bleeding (subdural, subarachnoid, intraparenchymal bleeding),GI bleed requiring transfusion,Bleeding from other sites requiring transfusion) Psychosocial reasons that make study participation impractical Currently enrolled in another IND or IDE trial that has not completed the primary endpoint or that clinically interferes with the current study endpoints Co-morbid condition(s) that could limit the subject's ability to participate in the trial or to comply with follow-up requirements, or that could impact the scientific integrity of the study. Prisoners or subjects who are involuntarily incarcerated Subjects who are compulsorily detained for treatment of either psychiatric or physical illness Current or expected systemic treatment with strong dual inhibitors of CYP3A4 and P-gp (Any one of rifampin, carbamazepine, phenytoin, St. John's Wort, ketoconazole, itraconazole, ritonavir, clarithromycin) Need for dual anti-platelet therapy with aspirin and another agent such as thienopyridine

Ages Eligible for Study
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Minimum Age: 60 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Eliquis<br> | Drug: Apixaban<br>* Dosage either 5mg or 2.5mg for 2 years<br>* Other names: Eliquis;|
| Active Comparator: Warfarin<br> | Drug: Warfarin<br>* Dosage assessed by your treating physician for 2 years<br>* Other names: Coumadin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Standardized Neurocognitive Function Score | Assess the change in cognitive function using standardized neurocognitive assessment. | Baseline, Year 1, Year 2 | 
| MRI Evidence of Silent Cerebral Infarct | Magnetic Resonance Imagining of the brain to assess the development of new silent cerebral infarcts. | Baseline, Year 2 | 
| MRI Evidence of New Cerebral Micro-bleeds | Magnetic Resonance Imagining of the brain to assess the development of new cerebral micro-bleeds | Baseline, Year 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Apixaban, Warfarin