Apixaban for Secondary Prevention of Thromboembolism Among Patients With AntiphosPholipid Syndrome

Inclusion Criteria: 1. Be ≥ 18 years of age 2. Have a clinical diagnosis of the antiphospholipid syndrome (APS) and a history of venous thrombosis only (excluding arterial thrombosis as recommended by the Data Safety Monitoring Board (DSMB)) for which the patient is receiving anticoagulation therapy for the prevention of recurrent thrombosis; 1. Anticoagulation is defined as warfarin sodium titrated at the discretion of the clinician to a target INR (International Normalized Ratio) 2.5 (range 2-3), 3.0 (range 2.5-3.5), or 3.5 (range 3-4). 2. Should the patient be receiving some other form of anticoagulation (apixaban, rivaroxaban, edoxaban, dabigatran etexilate, low-molecular weight heparin) and is willing to be randomized to warfarin with a target INR 2.5 or apixaban 5 mg by mouth twice daily and meets all other inclusion criteria. 3. Able to undergo magnetic resonance imaging (MRI) of the brain; 4. Have completed at least 6 months of anticoagulation for the indication of venous thrombosis and be without symptoms or signs consistent with acute thrombosis for a minimum of 6 months; 5. Be willing to provide informed consent to contact the subjects anticoagulation provider for INRs and dosing as well as details regarding any adverse events; 6. A woman of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of hCG (Human Chorionic Gonadotropin) within 24 hours prior to the start of study drug; 7. Women must not be breastfeeding; 8. A WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug apixaban plus 5 half-lives of study drug apixaban (3 days) plus 30 days (duration of ovulatory cycle) for a total of 33 days post-treatment completion; 9. Males who are sexually active with any WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug apixaban plus 5 half-lives of the study drug apixaban (3 days) plus 90 days (duration of sperm turnover) for a total of 93 days post-treatment completion; 10. Azoospermic males and women who are continuously not heterosexually active are exempt from contraceptive requirements. However, a WOCBP must still undergo pregnancy testing as described above; 11. If they are actively receiving a strong dual inhibitor of cytochrome P450 3A4 (CYP3A4) and P-gp, such as ketoconazole, itraconazole, ritonavir, and are agreeable to taking apixaban 2.5 mg twice daily. Exclusion Criteria: 1. A history of arterial thromboembolism (e.g., stroke, myocardial infarction, or other arterial thrombosis); 2. Another indication for long-term anticoagulation for which no FDA (Food \& Drug Administration) approval of apixaban exists (e.g., mechanical heart valve); 3. A life expectancy of less than 1 year; 4. Is unable to attend follow-up appointments; 5. Is participating in a clinical trial or has participated in a trial within the last 30 days; 6. Is receiving concomitant dual antiplatelet therapy; 7. Requires aspirin dose of greater than 165 mg daily; 8. Requires clopidogrel, ticagrelor, prasugrel, or another P2Y12 inhibitor; 9. A hemoglobin level of less than 8 mg per deciliter; 10. A platelet count of less than 50,000 per cubic millimeter; 11. Serum creatinine level of more than 2.5 mg per deciliter or a calculated creatinine clearance of less than 25 ml per minute; 12. Alanine aminotransferase or aspartate aminotransferase level greater than 2 times the upper limit of the normal range; 13. A total bilirubin more than 1.5 times the upper limit of the normal range; 14. Have active cancer for which treatment (chemotherapy/radiation therapy) is being delivered or has been delivered within the last 3 months; 15. Are actively taking a strong dual inducer of CYP3A4 and P-gp, such as: * rifampin * carbamazepine * phenytoin * St.John's wort 16. Intend pregnancy or breastfeeding within the next year; 17. Have a known allergy to apixaban, rivaroxaban, or edoxaban; 18. Have experienced thrombosis while receiving warfarin at a target INR of 2 to 3 and have been assigned a higher target INR at the discretion of the treating clinician; 19. Have active pathological bleeding; 20. Have a history of catastrophic APS (CAPS) as defined by clinical routine; 21. At the discretion of the investigator, are not considered to be good candidates secondary to a safety concern. Patients who meet the above inclusion \& exclusion criteria will be offered participation in the study. After informed consent is obtained, the patient will be consented for Magnetic Resonance Imaging (MRI). A brain MRI without contrast including weighted imaging and fluid-attenuated inversion recovery (FLAIR) will be performed as a study procedure to rule out prior stroke. If the patient has radiographic evidence of prior stroke on this MRI, then the patient will not be randomized, and will not be included in future study procedures or study analyses.