Famotidine for the Prevention of Peptic Ulcers in Users of Low-Dose Aspirin - FAMOUS

Description:

The goal of the trial was to evaluate treatment with famotidine compared with placebo among patients taking low-dose aspirin.

Hypothesis:

Famotidine would be more effective in preventing peptic ulcers.

Study Design

  • Placebo Controlled
  • Randomized
  • Blinded
  • Parallel

Patients Screened: 14,515
Patients Enrolled: 404
Mean Follow Up: 12 weeks
Mean Patient Age: 63 years
Female: 32%

Patient Populations:

  • Patients at least 18 years of age on aspirin therapy for coronary, cerebrovascular, or peripheral arterial disease

Exclusions:

  • Malignancy
  • History of esophageal, gastric, or duodenal surgery
  • Zollinger-Ellison syndrome
  • Primary esophageal dismotility disorder
  • Pregnant or lactating women
  • Contraindication to the study medication
  • Use of proton-pump inhibitor, H2-receptor antagonist, or sucralfate within a week of baseline endoscopy
  • Treatment of Helicobacter pylori
  • Use of other investigation drugs, anticholinergic drugs, prostaglandin analogues, warfarin, high-dose steroids, cytotoxic drugs, nonsteroidal anti-inflammatory drugs, or bisphosphonates

Primary Endpoints:

  • Gastric or duodenal ulcer (≥3 mm) or erosive esophagitis at 12-week endoscopy

Secondary Endpoints:

  • Lanza scores for gastric and duodenal erosions
  • Adominal and vascular symptom scores
  • Overall treatment assessment
  • Antacid consumption

Drug/Procedures Used:

Patients taking low-dose aspirin without evidence of peptic ulcer disease at baseline endoscopy were randomized to famotidine 20 mg twice daily (n = 204) versus placebo twice daily (n = 200). Follow-up endoscopy was performed at 12 weeks.

Concomitant Medications:

There was no difference in baseline medication use between the groups. In the famotidine group, the use of clopidogrel was 19%, dipyridamole was 6%, beta-blocker was 62%, angiotensin-converting enzyme inhibitor was 54%, and nitrate was 42%.

Principal Findings:

Overall, 404 patients were randomized. There was no difference in baseline characteristics between the groups. In the famotidine group, the mean age was 63 years, 32% were women, duration of aspirin use was 3 years (97% were on 75 mg daily), 19% had diabetes, and 16% had cerebrovascular disease.

The occurrence of gastric ulcer at 12-week endoscopy was 3.4% in the famotidine group versus 15% in the placebo group (p = 0.0002), duodenal ulcer was 0.5% versus 8.5% (p = 0.0045), and erosive esophagitis was 4.4% versus 19% (p < 0.0001), respectively. There were nine adverse events in the famotidine group (no upper gastrointestinal [GI] hemorrhage) and 15 in the placebo group (four upper GI hemorrhage), with none attributed to be due to the study drug. After controlling for the use of famotidine, beta-blockers appeared to increase the incidence of peptic ulcers or esophagitis (odds ratio 2.6, p = 0.0017).

Interpretation:

Among patients taking aspirin, the use of 12 weeks of famotidine 20 mg twice daily is beneficial. This therapy reduced the incidence of peptic ulcer or esophagitis during follow-up endoscopy. This trial was not powered to examine clinical events; however, there were no episodes of GI hemorrhage in the famotidine group compared with four in the placebo group.

Omeprazole 20 mg daily has also been shown to reduce the incidence of peptic ulcers among aspirin users in the ASTERIX trial, although the relative benefit of famotidine versus omeprazole is unknown. Further study is needed of the optimal way to reduce GI bleeding in patients on antiplatelet therapy.

References:

Taha AS, McCloskey C, Prasad R, Bezlyak V. Famotidine for the prevention of peptic ulcers and oesophagitis in patients taking low-dose aspirin (FAMOUS): a phase III, randomized, double-blind, placebo-controlled trial. Lancet 2009;374:119-25.

Clinical Topics: Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Novel Agents

Keywords: Esophagitis, Odds Ratio, Follow-Up Studies, Coronary Disease, Endoscopy, Peripheral Arterial Disease, Gastrointestinal Hemorrhage, Stomach Ulcer, Duodenal Ulcer, Famotidine, Omeprazole, Peptic Ulcer, Diabetes Mellitus


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