Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation

Inclusion Criteria:

1. Signed Written Informed Consent
2. Males and Females over 18 years of age.
3. History of Nonvalvular Atrial Fibrillation (NVAF) by documentation in the medicalhistory or newly diagnosed nonvalvular Atrial Fibrillation at time of studyrandomization by ECG, device or telemetry .
4. Diagnosis of TIA or small or medium ischemic stroke 0 to 48 hours from signs orsymptoms.
5. Women of child-bearing potential must use a reliable method of contraception and mustprovide a negative pregnancy test at entry into the study and within 24 hours of studytreatment initiation.
6. WOCBP must agree to follow instructions for method(s) of contraception for theduration of treatment with study drug Apixaban plus 5 half-lives (approximately 3days) plus 30 days (duration of ovulatory cycle) for a total of 33 days post-treatmentcompletion.
7. Males who are sexually active with WOCBP must agree to follow instructions formethod(s) of contraception for the duration of treatment with Apixaban plus 5half-lives (approximately 3 days) plus 90 days (duration of sperm turnover) for atotal of 93 days post-treatment completion.
8. Azoospermic males and WOCBP who are continuously not heterosexually active are exemptfrom contraceptive requirements. However they must still undergo pregnancy testing asdescribed in this section. Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP onthe importance of pregnancy prevention and the implications of an unexpected pregnancyInvestigators shall advise WOCBP and male subjects who are sexually active with WOCBP onthe use of highly effective methods of contraception. Highly effective methods ofcontraception have a failure rate of < 1% when used consistently and correctly. At a minimum, subjects must agree to the use of one method of highly effectivecontraception as listed below: HIGHLY EFFECTIVE METHODS OF CONTRACEPTION

• Male condoms with spermicide
• Hormonal methods of contraception including combined oral contraceptive pills, vaginalring, injectables, implants and intrauterine devices (IUDs) such as Mirena by WOCBPsubject or male subject's WOCBP partner. Female partners of male subjectsparticipating in the study may use hormone based contraceptives as one of theacceptable methods of contraception since they will not be receiving study drug
• IUDs, such as ParaGard™
• Tubal ligation
• Vasectomy.
• Complete Abstinence

Exclusion Criteria:

1. Hemorrhagic stroke
2. Large ischemic stroke
3. History of major bleeding within the last 6 months from time of subject enrollment (e.g. GI bleed).
4. History of intracranial bleed a. Traumatic intracranial bleed within one year of randomization. (Traumatic ICHgreater than one year of randomization is not an exclusion).
5. Current or history of bleeding disorders (e.g. blood dycrasias)
6. Blood Pressure of 180/100 mmHg on hypertensive therapy day of randomization per PIdiscretion 20.
7. Current illicit drug use and/or chronic alcohol use per PI discretion.
8. Severe liver disease (AST/ALT 2x upper limit).
9. Patients with kidney disease meeting criteria to take 2.5 mg twice daily who aretaking strong dual inhibitors of CYP3A4 and P-glycoprotein (e.g. ketoconazole,itraconazole, ritonavir, clarithromycin) .
10. Any other suspected etiology for stroke (e.g. ipsilateral carotid disease).
11. Greater than 3 Cerebral Micro-bleeds (CMB) on gradient recovery echo (GRE) or evidenceof intracranial hemorrhage on CT at time of randomization. (SWI sequencing may be usedif GRE sequencing is not obtainable)
12. Therapeutically anti-coagulated at time of admission (INR at admission greater than 2.0 on warfarin or took two consecutive doses of NOAC).
13. Absolute indication for use of warfarin only.( e.g. Mechanical Valve)
14. Absolute indication for anticoagulation prior to randomization window. (e.g. DVT)
15. Hemoglobin less than 9 gm/dl and/or platelet count less than 100 K/uL.
16. Requires dual antiplatelet therapy.
17. Daily use of NSAIDS
18. Pregnancy or lactation.
19. Any use of an investigational product within the past 30 days.
20. Prisoners or subjects who are involuntarily incarcerated.
21. Subjects who are compulsorily detained for treatment of either a psychiatric orphysical (eg, infectious disease) illness.
22. Concurrent participation in another clinical study where use of an investigationalproduct is used