Clopidogrel and the Optimization of Gastrointestinal Events (COGENT-1)

Inclusion Criteria: * Patients in whom a requirement for clopidogrel therapy with concomitant aspirin is anticipated for at least the next 12 months. Specific conditions that may confer a need for long-term clopidogrel + aspirin therapy may include non-ST segment elevation acute coronary syndrome (unstable angina/non-Q-wave MI), ST segment elevation acute MI), or new placement of a coronary artery stent. * For women of childbearing potential, negative pregnancy test prior to randomization and agreement to use effective method of birth control during the study. * Able to provide written informed consent based on competent mental status. Exclusion Criteria: * Patients currently hospitalized for whom discharge is not anticipated within 48 hours of randomization. * Requirement for current or chronic use of a proton pump inhibitor, H2 receptor blocker, sucralfate or misoprostol. * Erosive esophagitis, esophageal or gastric variceal disease, or non-endoscopic gastric surgery. Patients with a history of GERD/erosive esophagitis or dyspepsia who do not currently require proton pump blockers will be eligible. * Receipt of \> 21 days of clopidogrel or another thienopyridine prior to randomization. * Oral anticoagulation that cannot be safely discontinued for duration of study. * Recent fibrinolytic therapy. * Scheduled percutaneous coronary intervention (PCI). Patients may be enrolled upon completion of PCI. * Recent (\< 30 days prior to randomization) or scheduled coronary artery bypass graft (CABG) surgery. * Cardiogenic shock at time of randomization, refractory ventricular arrhythmias, or congestive heart failure (NY Heart Association class IV). * Active pathological bleeding or a history of hereditary or acquired hemostatic disorder. * History of hemorrhagic stroke, intracranial neoplasm, arteriovenous malformation or aneurysm. * Systemic corticosteroids except low-dose oral corticosteroids equivalent to prednisone \< or equal to 5 mg/day. * Allergy or contraindication to clopidogrel or other thienopyridine drugs, omeprazole or other proton pump inhibitor drugs, aspirin or salicylate derivatives, or other study drug ingredients. * Treatment within 30 days prior to randomization with any investigational drug or device including investigational coronary artery stents or currently enrolled in another interventional drug or device study. * Women who are pregnant or breastfeeding. * Life expectancy less than 12 months. * Laboratory abnormality at screening that is clinically significant or outside protocol-allowed limits, or any other condition that precludes participation in the study in the opinion of the Investigator.