Randomized On-X Anticoagulation Trial

This is a longitudinal, randomized (randomization to occur at the 3-month follow-up) study
comparing the On-X valve on low dose anticoagulation (test group) to concomitant control
groups of On-X valves receiving standard Coumadin/aspirin therapy, and also to FDA objective
performance criteria (OPC) for heart valve replacement. It is a multicenter study consisting
of up to 50 centers in the United States, Canada, and Italy enrolling and randomizing no more
than 1200 patients (200 in each of 6 groups). There are three test arms of the study: low
risk aortic valve replacement, high risk aortic valve replacement, and mitral valve
replacement. Each arm has an equivalent control. Test therapies are: low risk aortic valve
replacement - aspirin/Plavix, high risk aortic valve replacement - Coumadin at INR of 1.5 to
2.0 plus aspirin, and mitral valve replacement - Coumadin at an INR of 2.0 to 2.5 plus
aspirin. Follow-up will run for up to 8 years in each patient. Each arm is independent and
the low risk aortic and high risk aortic arms are completed. The low risk aortic arm was
closed early resulting in a reduction of the estimated total enrollment with randomization to
1000. The high risk arm is completed with FDA review and this arm had 375 randomized
enrollees. The mitral arm continues to enroll with a planned randomized enrollment of 400.

Inclusion Criteria:

- Patients requiring isolated aortic valve replacement (AVR), or isolated mitral valve
replacement (MVR).

- AVR patients receiving low dose or antiplatelet only anticoagulation will be divided
into groups at low risk and high risk for thromboembolism with all patients being in
the low risk group except for patients with the following conditions which place a
patient in the high risk group:

- Chronic atrial fibrillation

- Left ventricular ejection fraction < 30 %

- Enlarged left atrium >50mm diameter

- Spontaneous echo contrasts in the left atrium

- Vascular pathology

- Neurological events

- Hypercoagulability

- Left or right ventricular aneurysm

- Lack of platelet response to aspirin or clopidogrel

- Women receiving estrogen replacement therapy

- Concomitant cardiac surgery is allowed

- Adult patients

Exclusion Criteria:

- Right side valve replacement

- Double (aortic plus mitral) valve replacement

- Patients with active endocarditis at the time of implant

- Previous confirmed or suspected thromboembolic event or thrombophlebitis

- Other terminal illness

- Patients who are in an emergency state

- Inability to return for required follow-ups

- Patients with an On-X valve implanted within the study and subsequently explanted

- Patients who are known to be pregnant, plan to become pregnant or are lactating

- Patients with acquired immunodeficiency syndrome or know to be HIV positive

- Patients who are prison inmates or known drug or alcohol abusers

- Patients unable to give adequate informed consent.