Inclusion Criteria:

1. Patients with one or more of the following indications for chronic warfarin anticoagulation (the patient may either be a new candidate for anticoagulation or may already be receiving warfarin):

   1. Atrial fibrillation (paroxysmal, persistent or permanent, not due to a reversible cause, documented by ECG) or atrial flutter.
   2. A prosthetic heart valve in the aortic or mitral position that requires chronic anticoagulation.
   3. A history of venous thromboembolic disease (DVT and/or PE) requiring long term anticoagulation (> 6 months).
   4. A history of myocardial infarction or cardiomyopathy requiring anticoagulation.
   5. Currently receiving chronic warfarin therapy for another indication not listed, with Sponsor approval.
2. Male or female greater than 18 years of age.
3. Able and willing to sign IRB approved written informed consent to participate in the study.
4. Able and willing to follow instructions, to comply with protocol requirements, and to attend required study visits.

Exclusion Criteria:

1. Contraindications to anticoagulation as listed in the warfarin package insert (Appendix D), such as active bleeding or lesions at risk of bleeding such as gastric ulceration, colonic or cerebral AV malformations, cerebral or aortic aneurysms, pericarditis or endocarditis. Patients who have had recent (< 14 days from screening) surgery or invasive procedures or are about to undergo surgery or other invasive procedures, such as lumbar puncture. Patients with blood dyscrasias or inherited disorders of hemostasis. Patients with a history of hemorrhagic tendencies or prior serious hemorrhagic events such as hemorrhage within the cranium, eye, spinal cord, retroperitoneum, or gastrointestinal tract.
2. Laboratory evidence at screening of clinically significant active bleeding, such as unexplained positive occult blood in stool, or unexplained positive urinary blood that is more than trace positive for hemoglobin.
3. Concomitant use of other anticoagulant or antiplatelet agents that may add to the hemostatic burden such as clopidogrel, ticlopidine, heparin or low molecular weight heparin (LMWH), or regular use of non selective long acting NSAIDs that cannot be discontinued prior to initiating ATI 5923/warfarin dosing (daily use of 81-100 mg aspirin is allowed).
4. A life expectancy of < 1 year, end stage renal failure requiring dialysis, end stage pulmonary disease requiring home oxygen, severe heart failure (NYHA class IV).
5. Dementia, severe psychiatric disorder, or ongoing alcohol or substance abuse.
6. Laboratory screening values indicating severe anemia (Hb < 10 gm/L), thrombocytopenia (platelet count < 90,000/mcL), or active liver disease.
7. Patients with conditions that will interfere with determination of the INR using the INRatio device, i.e., hematocrit <30% or >55%. Patients with the antiphospholipid syndrome may have abnormal INR results and should not be enrolled.
8. History of non disabling ischemic stroke within the last 3 months, prior major disabling ischemic stroke, or any history of intracranial bleeding.
9. Pregnant or nursing women or women of childbearing potential who will not use adequate contraception, such as oral or implantable contraceptives, IUD, or barrier methods (IUD or condom) with spermicide.
10. Currently participating in another clinical trial at screening, treatment with an investigational drug within 30 days of the first dose of study medication, or patients who previously participated in an ATI-5923 trial.