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

J Gastroenterol Hepatol. 2019 Sep;34(9):1517-1522. doi: 10.1111/jgh.14671. Epub 2019 May 8.

Abstract

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).

Keywords: dual antiplatelet; peptic ulcer; prevention.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Alanine / administration & dosage
  • Alanine / adverse effects
  • Alanine / analogs & derivatives*
  • Anti-Ulcer Agents / administration & dosage*
  • Anti-Ulcer Agents / adverse effects
  • Aspirin / administration & dosage
  • Aspirin / adverse effects*
  • Cilostazol / administration & dosage
  • Cilostazol / adverse effects*
  • Clopidogrel / administration & dosage
  • Clopidogrel / adverse effects*
  • Cytoprotection
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptic Ulcer / chemically induced
  • Peptic Ulcer / pathology
  • Peptic Ulcer / prevention & control*
  • Percutaneous Coronary Intervention
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects*
  • Quinolones / administration & dosage*
  • Quinolones / adverse effects
  • Thailand
  • Ticagrelor / administration & dosage
  • Ticagrelor / adverse effects*
  • Time Factors
  • Treatment Outcome

Substances

  • Anti-Ulcer Agents
  • Platelet Aggregation Inhibitors
  • Quinolones
  • Clopidogrel
  • Ticagrelor
  • rebamipide
  • Cilostazol
  • Alanine
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT02166008