Investigation of the Athero-Protective Effects of Clopidogrel

Blockages in the blood vessels of the heart are caused by atherosclerosis. Atherosclerosis is the main cause for chest pain and heart attacks. Gradual narrowing of the vessels of the heart caused by blockages causes chronic symptoms, such as chest pain. Those with these findings often have a cardiac catheterization to detect these blockages. Additionally these patients may have an angioplasty or stent placed to help relieve these symptoms. With this angioplasty/stent procedure, patients are placed on the drug clopidogrel to help prevent clots from forming and narrowing of the blood vessels. Clopidogrel is a blood thinner that prevents clots from forming similar to an aspirin, but is more powerful and effective. Markers, or substances, have been identified that cause worsening of the blockages in the blood vessels of the heart. Many of these substances have been shown to decrease with the use of clopidogrel. This occurs separately from clopidogrel's ability to prevent clots. Endothelial progenitor cells, or EPCs, come mostly from the bone marrow and is helpful in repairing damage to the lining of the blood vessels of the heart. The EPCs help balance out the damage incurred in the blood vessels from those harmful markers. Several other drugs commonly used in heart disease have recently been shown to improve EPCs function. With this in mind, it is important to understand more of clopidogrel's function. A decrease in markers that cause worsening of the blockages, and an increase in the number of cells that will help repair damaged blood vessels of the heart is important in avoiding future chest pain and heart attacks. This may be how clopidogrel is currently protecting patients from developing new blockages. The investigators would like to investigate whether clopidogrel will help lower the level of harmful markers in patients with coronary artery disease, and at the same time will help increase the cells that are useful in repairing the damaged blood vessels. The investigators will give half of the patients clopidogrel and the other half a sugar pill, placebo, and check the levels of these markers and helpful cells in each group. At the same time the investigators will check how well these patient's blood vessels work using ultrasound imaging of the forearm to see how blood vessels relax and tonometry to see how stiff the patient's blood vessels are. After 6 weeks of drug therapy, the patients will switch to the other drug and these same tests will be performed after an additional 6 weeks of therapy. The drug taken by the patient will not be known to the patient or the researchers. The patients will continue on their prescribed medical therapy during the duration of the 12 week study.

Inclusion criteria

• Male or females without child bearing potential aged 21-80 years
• Known coronary artery disease by angiogram or documented myocardial infarction.
• Able to provide written informed consent

Exclusion criteria

• Treated with clopidogrel or ticlodipine in the previous 3 months
• Age < 21 or >80 years
• Premenopausal females with potential for pregnancy
• Allergy to clopidogrel or aspirin
• Initiation or change in dose of any concomitant medical therapy within 2 months before the study
• Uncontrolled hypertension with BP>180 mmHg systolic and >120 mmHg diastolic
• Treated with coumadin therapy
• Intolerance or allergy to statins
• Acute infection in previous 4 weeks
• History of substance abuse
• Uninterpretable PAT test
• Current neoplasm
• Chronic renal failure [creatinine > 2.5 mg/dL] or liver failure (Liver enzymes >2X normal)
• Acute coronary syndrome, heart failure, CVA, coronary intervention within 3 months
• Known aortic stenosis, hypertrophic cardiomyopathy, symptomatic heart failure.
• Inability to give informed consent
• Inability to return to Emory for follow-up