Aspirin therapy is frequently recommended for the secondary prevention of cardiovascular events. The known benefits of aspirin and ease of accessibility have led to its increased use.1 A major factor associated with peptic ulcer disease is the use of non-steroidal anti-inflammatory drugs, such as aspirin. Aspirin affects the normal mucosal defense and healing mechanisms of the gastrointestinal (GI) system leading to peptic ulcers and esophagitis.2 Currently, the standard of care for prevention and treatment of peptic ulcers is the use of proton pump inhibitors (PPIs). However, due to current controversies surrounding the use of PPIs and clopidogrel, researchers are looking at alternative agents, such as histamine-2 (H2) antagonists. Recently, famotidine, a H2 antagonist, was evaluated for the prevention of peptic ulcers and esophagitis.
The FAMOUS (Famotidine for the Prevention of Peptic Ulcers in Users of Low-dose Aspirin) study was a randomized, double-blind, placebo-controlled, phase III clinical trial. Adult participants (>18 years) were enrolled if they had a stable indication for long-term treatment (≥12 weeks) with low-dose aspirin (75-325 mg daily). Stable indications that necessitated aspirin therapy for inclusion into the study included: angina, previous myocardial infarction (≥12 weeks before recruitment), cerebrovascular disease, diabetes, or peripheral vascular disease. Patients were allowed to continue all other medications for any coexisting medical conditions, including clopidogrel and dipyridamole. Those excluded were either pregnant, lactating, or had any malignancy, prior upper gastrointestinal or duodenal surgery, Zollinger-Ellison Syndrome, or primary esophageal motility disorder. Patients were also excluded if they used PPIs, H2 antagonists, or sucralfate within one week of the first endoscopic assessment, or if the patient was ever treated for Helicobacter pylori. The primary outcome was the development of new ulcers (size ≥3 mm) in the stomach or duodenum or erosive esophagitis at 12 weeks. The secondary outcomes included Lanza scores for gastric and duodenal erosions, abdominal and vascular symptoms score, overall treatment assessment, and antacid consumption.
Of 14,515 patients assessed for eligibility, only 404 patients were enrolled and randomized to receive a 20 mg tablet of famotidine (n = 204) or placebo (n = 200), both given twice daily. There were no significant baseline differences between the two comparator groups. The median age was 63 years. 277 (68.6%) of patients were male. Enrolled patients were analyzed by intention to treat and per protocol. All patients were required to have an endoscopic assessment performed at baseline and at 12 weeks. A clinical assessment was also performed at baseline, 6 weeks, and 12 weeks after randomization.
The endoscopic results at 12 weeks revealed that 5.9% (n = 12) of patients in the famotidine group experienced erosive esophagitis and/or ulcer ≥3 mm versus 33% (n = 66) in the placebo group. More specifically the gastric ulcers developed in 3.4% of patients receiving famotidine compared to 15% of those taking placebo, duodenal ulcer developed in 0.5% versus 8.5%, and erosive esophagitis in 4.4% versus 19%, respectively. There were no significant differences found in secondary outcomes.
The authors concluded that famotidine is effective in the prevention of ...