Cytoprotective agent for peptic ulcer prevention in patients taking dual antiplatelet agents: A randomized, double-blind placebo-controlled trial

Background and Aim Long-term use of dual antiplatelets is increasing, and most patients need primary peptic ulcer prophylaxis. The long-term use of proton pump inhibitors (PPIs) is associated with adverse events. We evaluated the efficacy of rebamipide for peptic ulcer prevention. Methods This randomized controlled trial was conducted between July 2014 and November 2017. Patients receiving dual antiplatelets for >= 1 year with no history of peptic ulcer bleeding or perforation were recruited and randomly assigned to the rebamipide (300 mg/day) group or the placebo group. Patients who used proton pump inhibitors were excluded. The primary endpoint was a new mucosal break on esophagogastroduodenoscopy at 3 or 12 months after treatment initiation. The secondary endpoints were hematocrit changes from the baseline, gastrointestinal bleeding, and chest pain. Antiplatelet function was assessed. Results In total, 95 eligible patients were identified; 12 were excluded, and 83 patients were randomized, with 66 (79.5%) and 59 (71.1%) patients eligible at the 3- and 12-month follow ups, respectively. The baseline characteristics were equivalent between the groups. During the 12 months of follow up, 13 patients (43.3%) taking rebamipide and 19 (65.5%) taking the placebo experienced mucosal injury (P = 0.07). Two patients (6.7%) taking rebamipide and eight (27.6%) taking the placebo had peptic ulcers >= 5 mm or < 5 mm with pigmented spots (P = 0.03). The changes in hematocrit were not different between the two groups. Neither bleeding ulcers nor chest pain was observed. Conclusion Rebamipide is safe and may prevent peptic ulcers >= 5 mm in diameter or those with pigmented spots in patients receiving dual antiplatelets for 1 year (NCT02166008).