A Study of Apixaban in Patients With Atrial Fibrillation, Not Caused by a Heart Valve Problem, Who Are at Risk for Thrombosis (Blood Clots) Due to Having Had a Recent Coronary Event, Such as a Heart Attack or a Procedure to Open the Vessels of the Heart

Study Overview
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Brief Summary
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The purpose of this study is to determine if Apixaban is safer than a Vitamin K Antagonist given for 6 months in terms of bleeding in patients with an irregular heart beat (atrial fibrillation) and a recent heart attack or a recent procedure to open up a blood vessel in the heart. All patients would also be taking a class of medicines called P2Y12 inhibitors (such as clopidogrel/Plavix) and be treated for up to 6 months. The primary focus will be a comparison of the bleeding risk of Apixaban, with or without aspirin, versus a Vitamin K antagonist, such as warfarin, with or without aspirin.

Detailed Description
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Patients will be recruited from either inpatient coronary care or general medical units, or recruited from outpatient cardiology offices. Masking: Apixaban: Open label. VKA: Open label. Acetylsalicylic acid film coated tablet: Double Blinded. Placebo matching Acetylsalicylic acid film coated tablet: Double Blinded.

Official Title
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An Open-label, 2 x 2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention

Conditions
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Acute Coronary Syndromes

Intervention / Treatment
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* Drug: Apixaban
* Drug: vitamin K antagonist
* Drug: Acetylsalicylic acid
* Other: Acetylsalicylic acid placebo


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Adults with either active or a history of non-valvular atrial fibrillation or flutter with the planned or existing use of an oral anticoagulant for prophylaxis of thromboembolism. In addition, subjects must have had an acute coronary syndrome or percutaneous coronary intervention with a stent within the prior 14 days Planned use of antiplatelet agents for at least 1 to 6 months Males and Females ≥ 18 years of age Women of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug Exclusion Criteria: Conditions other than atrial fibrillation that require chronic anticoagulation. (e.g. prosthetic mechanical heart valve) Severe renal insufficiency (serum creatinine > 2.5 mg/dL or a calculated creatinine clearance < 30 mL/min Patients with a history of intracranial hemorrhage Patients have had or will undergo Coronary arterial bypass graft (CABG) for their index acute coronary syndrome (ACS) event Patients with known ongoing bleeding and patients with known coagulopathies Any contraindications or allergies to VKA, apixaban, or to intended P2Y12 antagonists or to aspirin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 95 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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Apixaban<br>5 mg or 2.5 mg Apixaban tablets orally twice per day | Drug: Apixaban<br> <br> * Other names: BMS-562247;|
| Active Comparator: Vitamin K Antagonist<br>VKA tablets orally once daily | Drug: vitamin K antagonist<br> <br> |
| Placebo Comparator: Acetylsalicylic acid film coated tablet<br>81 mg Acetylsalicylic acid film coated tablet orally once daily | Drug: Acetylsalicylic acid<br> <br> * Other names: Aspirin 81 mg;|
| Placebo Comparator: Placebo matching Acetylsalicylic acid film coated tablet<br>Placebo matching Acetylsalicylic acid film coated tablet once daily | Other: Acetylsalicylic acid placebo<br> <br> * Other names: aspirin placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Rate of International Society on Thrombosis and Haemostasis (ISTH) Major or Clinically Relevant Non-Major (CRNM) Bleeding With Apixaban Versus Vitamin K Antagonist (VKA) During the Treatment Period | Time to first ISTH major or CRNM bleeding during the 6-month period of treatment with Apixaban or VKA. N is the number of participants treated with Apixaban or VKA. n is the number of participants treated with Apixaban or VKA with major or CRNM bleeding in each treatment group during the 6-month period of treatment. Event rates are calculated based on the number of participants with major or CRNM bleeding divided by the sum of the number of days from the first dose of study drug to the event date or censoring date and expressed as percentage per year. | Approximately 6 months | 
| The Rate of ISTH Major or CRNM Bleeding With Aspirin Versus no Aspirin During the Treatment Period | Time to first ISTH major or CRNM bleeding during the treatment period of 6 months with aspirin or placebo. N is the number of participants with aspirin or placebo. n is the number of participants treated with aspirin or placebo with major or CRNM bleeding in each treatment group during the 6-month period of treatment. Event rates are calculated based on the number of participants with event of interest divided by the sum of the number of days from the first dose of study drug to the event date or censoring date and expressed as percentage per year. | Approximately 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Superiority on ISTH Major or CRNM Bleeding for Apixaban Versus VKA | Time to first occurrence during the time the participants were treated with Apixaban or VKA. N is the number of participants treated with Apixaban or VKA. n is the number of participants treated with Apixaban or VKA with major or CRNM bleeding in each treatment group during the 6-month period of treatment. Event rates are calculated based on the number of participants with event of interest divided by the sum of the number of days from the first dose of study drug to the event date or censoring date and expressed as percentage per year. | Approximately 6 months | 
| The Rate of All-cause Death or All-cause Rehospitalization With Apixaban Versus VKA | Time to first all-cause death or all-cause hospitalization during the during the 6-month treatment period with Apixaban or VKA. N is the number of participants treated with Apixaban or VKA. n is the number of participants treated with Apixaban or VKA with all-cause death or all-cause hospitalization in each treatment group during the 6-month period of treatment. Event rates are calculated based on the number of participants with all-cause death or all-cause hospitalization divided by the sum of the number of days from the first dose of study drug to the event date or censoring date and expressed as percentage per year. | Approximately 6 months | 
| The Rate of All-cause Death or All-cause Rehospitalization With Aspirn Versus no Aspirin | Time to first all-cause death or all-cause hospitalization during the 6-month period of treatment with aspirin or placebo. N is the number of participants treated with aspirin or placebo. n is the number of participants treated with aspirin or placebo with all-cause death or all-cause hospitalization in each treatment group during the 6-month period of treatment. Event rates are calculated based on the number of participants with all-cause death or all-cause hospitalization divided by the sum of the number of days from the first dose of study drug to the event date or censoring date and expressed as percentage per year. | Approximately 6 months | 
| The Rate of the Composite Endpoint of Death or Ischemic Events (Stroke, Myocardial Infarction, Stent Thrombosis, Urgent Revascularization) With Apixaban Versus VKA | Time to first occurrence during the 6-month treatment period with Apixaban or VKA. N is the number of participants treated with Apixaban or VKA. n is the number of participants treated with Apixaban or VKA with death or ischemic events in each treatment group during the during the 6-month period of treatment. Event rates are calculated based on the number of participants with death or ischemic events divided by the sum of the number of days from the first dose of study drug to the event date or censoring date and expressed as percentage per year. | Approximately 6 months | 
| The Composite Endpoints of Death and Ischemic Events (Stroke, Myocardial Infarction, Stent Thrombosis, Urgent Revascularization) With Aspirin Versus no Aspirin | Time to first death or ischenic event during the 6-month treatment period with aspirin or placebo. N is the number of participants treated with aspirin or placebo. n is the number of participants treated with aspirin or placebo with death or ischemic events in each treatment group during the 6-month treatment period. Event rates are calculated based on the number of participants with death or ischemic events divided by the sum of the number of days from the first dose of study drug to the event date or censoring date and expressed as percentage per year. | Approximately 6 months |