Clopidogrel causes significantly less peptic ulcer disease (PUD) and ulcer bleeding than low-dose aspirin in general population. However, clopidogrel is not safe enough for gastrointestinal (GI) mucosa in patients who had past history of aspirin-associated ulcer or ulcer bleeding. Aspirin plus proton pump inhibitor (PPI) is superior to clopidogrel alone in preventing recurrent ulcer bleeding in these high risk patients.

This study is to compare the ulcer healing rate and ulcer bleeding at 12 weeks in patients with aspirin-associated PUD when they take PPI (rabeprazole 20 mg/day) to treat their PUD and simultaneously take aspirin or clopidogrel for their cardiovascular (CV) prevention. Two hundred patients will be randomly assigned rabeprazole (20 mg/day) plus aspirin (100 mg/day) or rabeprazole (20 mg/day) plus clopidogrel (75 mg/day) for 12 weeks. The primary end point is treatment success (ulcer healing rate). The secondary end point is incidence of ulcer bleeding within 12 weeks.

If rabeprazole plus aspirin in not inferior to rabeprazole plus clopidogrel in the incidence of ulcer healing and ulcer bleeding in the healing phase,PPI plus aspirin rather than PPI plus clopidogrel will be recommended during acute ulcer healing in patients who need antiplatelet therapy for their CV prevention.

Inclusion Criteria:

• Patients who have taken aspirin for more than 1 month and are found to have PUD by upper endoscopy will receive PPI (rabeprazole 20 mg once daily) to treat their PUD. PUD in the upper gastrointestinal (UGI) tract is defined as

  • [1] mucosal break of stomach or duodenum > 3 mm in diameter; or
  • [2] more than 10 gastric or duodenal erosions, without malignancy proved by histopathological examination.

Exclusion Criteria:

• Patients will be excluded if they have PUD with bleeding (ulcer with adherent blood clot, visible vessel, oozing, or spurting) requiring endoscopic hemostasis,
• if they take other antithrombotic or anticoagulants simultaneously, if they have take NSAIDs, selective COX-2 inhibitors, or steroid,
• if they have take misoprostol or histamine receptor-2 antagonist (H2RA),
• if they have bleeding tendency (thrombocytopenia with platelet count < 80000/mm3 or prolonged pro thrombin time > 5 seconds),
• if they have anemia (hemoglobin < 10 g/dL),
• if they have received a surgical intervention due to PUD complication (bleeding, perforation, obstruction) in the past,
• if their age are > 80 year-old or < 18 year-old,
• if they have severe cardiovascular, pulmonary, hepatic, or renal disease.