A  randomized controlled trial was carried to explore whether omeprazole (proton pump inhibitor) has superior efficacy compared to famotidine (histamine-2 receptor antagonists) to prevent mucosal breaks in 170 high-risk users of low-dose aspirin having a peptic ulcer history and who did not have mucosal breaks at initial endoscopy. 

Participants were randomly allocated to receive omeprazole (20 mg once a day, n=86) or famotidine (20 mg twice daily, n=84) for six months. The follow-up endoscopy was carried at the end of the sixth month and whenever hematemesis, epigastric discomfort, or melena occurred. The gastroduodenal mucosal break occurrence was the major endpoint. Secondary outcomes were the occurrence of gastroduodenal ulcers and gastroduodenal bleeding.

The incidence of gastroduodenal mucosal breaks was higher in famotidine-recipients compared to omeprazole recipients. The two groups had similar incidence rates of gastroduodenal ulcers, and gastroduodenal bleeding, as depicted below:

The multivariate analysis demonstrated that proton pump inhibitor use was an independent protective factor (odds ratio: 0.47). Smoking was found to be a pivotal risk factor for the occurrence of gastroduodenal mucosal breaks (odds ratio: 3.84).

Proton pump inhibitors have superior efficacy compared to histamine-2 receptor antagonists in preventing gastroduodenal mucosal breaks in high-risk aspirin users. For the occurrence of mucosal breaks, smoking is an independent risk factor.