To determine if prasugrel is superior to clopidogrel in providing adequate antiplatelet effect in a high risk population that requires concomitant use of a Proton Pump Inhibitor (PPI).

To evaluate if simultaneous treatment with the PPI omeprazole and a P2Y12 receptor antagonist will influence the effect of either clopidogrel and/or prasugrel on platelet reactivity in patients with Coronary Artery Disease (CAD) or Peripheral Arterial Disease (PAD).

Inclusion Criteria:

• Adults between 18 and 75 years of age
• Known or documented history of CAD or PAD prior to enrollment (a diagnosis of CAD may be based upon a positive stress test, prior documented acute coronary event, or angiographic demonstration of CAD; a diagnosis of PAD may be based upon an ankle-brachial index less than 0.9, or angiographic demonstration of PAD)
• Have not had thienopyridine therapy for at least 15 days before the study
• Have not had treatment with a PPI for at least 15 days before the study
• Are taking aspirin (75 to 325 mg/day) for at least one week prior to randomization

Exclusion Criteria:

• Have New York Heart association (NYHA) Class III and IV congestive heart failure

• Have any form of coronary revascularization (PCI or coronary artery bypass grafting [CABG]) planned to occur during the study

• Have undergone PCI or CABG within 30 days of entry to the study

• Have received a drug eluting endovascular stents in the past year

• Have any of the following:

  1. Prior history of hemorrhagic stroke or transient ischemic attack (TIA)
  2. Intracranial neoplasm, arteriovenous malformation, or aneurysm
  3. A body weight less than 60 kg

• Have prior history of GI ulcer disease or bleeding

• Have symptoms of dyspepsia or gastroesophageal reflux disease

• Have active internal bleeding or history of bleeding diathesis

• Have clinical findings, in the judgment of the investigator, associated with an increased risk of bleeding

• Have an International Normalized Ratio (INR) known to be >1.5 at the time of evaluation

• Have a platelet count of <100,000/mm3 at the time of screening, if known

• Have anemia (hemoglobin [Hgb] <10 gm/dL) at the time of screening, if known

• Are receiving or will receive oral anticoagulation or other antiplatelet therapy (other than aspirin) that cannot be safely discontinued for the duration of the study

• Are receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) that cannot be discontinued or require daily treatment with NSAIDs during the study.

• Are receiving corticosteroid therapy

Patients with Coronary or Peripheral Artery Disease