Pantoprazole to Prevents Gastroduodenal Events in Patients Receiving Rivaroxaban and/or Aspirin in a Randomized, Double-blind, Placebo-controlled Trial

Abstract Background & Aims Antiplatelet and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk. Methods We performed a 3x2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation. Results There was no significant difference in upper gastrointestinal events between the pantoprazole group (102/8791 events) and the placebo group (116/8807 events) (hazard ratio [HR], 0.88; 95% CI, 0.67–1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (HR, 0.52; 95% CI, 0.28–0.94; P =.03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (HR, 0.45; 95% CI, 0.27–0.74) although the number needed to treat still was high (982; 95% CI, 609–2528). Conclusions In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events but may reduce bleeding from gastroduodenal lesions. Clinicaltrials.gov no: NCT01776424