Famotidine Is Inferior to Pantoprazole in Preventing Recurrence of Aspirin-Related Peptic Ulcers or Erosions FOOK–HONG NG, SIU–YIN WONG, KWOK–FAI LAM, WAI–MING CHU, et al. GASTROENTEROLOGY 2010 ; 138 : 82 – 88 R3 Jung Kook Wi / Prof. Jae Young Jang

BACKGROUND Low-dose aspirin –Prevent cerebral and cardiovascular events in individuals with symptomatic atherothrombotic disease Limited by gastrointestinal side effects –Dyspepsia to life-threatening bleeding or perforation of GD ulcers The secondary prevention –Low-dose aspirin–induced symptomatic peptic ulcers or erosions in patients who need to continue aspirin –The best option  Eradication of H pylori infection & PPI use The role of H 2 -receptor antagonists (H2RAs) after healing of aspirin-induced peptic ulcers or erosions –Unclear ???

No randomized controlled trial with a clinical outcome The randomized controlled studies on the prevention of NSAIDs – Induced endoscopic gastroduodenal ulcer. –Famotidine for the prevention of gastric and duodenal ulcers caused by nonsteroidal antiinflammatory drugs. N Engl J Med 1996;334:1435–1439. –Famotidine for healing and maintenance in nonsteroidal anti-inflammatory drug-associated gastroduodenal ulceration. Gastroenterology 1997;112:1817–1822. In a Meta-analysis –Prevention of NSAID-induced gastroduodenal ulcers Cochrane Database Syst Rev 2002;4

AIMS The randomized, double-blind, controlled study To compare the efficacy of high-dose famotidine with pantoprazole in the prevention of recurrent dyspeptic or complicated ulcers/erosions in patients taking low-dose aspirin

Patients The Ruttonjee Hospital / August November 2008 Screening – A history of upper GI bleeding or dyspepsia due to peptic ulcers/erosions while receiving low-dose aspirin –Endoscopic gastric or duodenal ulcers or ≥ 5 erosions in the stomach or duodenum –Required continuous low-dose aspirin : mg for the secondary prevention of coronary heart disease, peripheral vascular disease, or ischemic stroke or TIA –≥ 18 years of age A mucosal break of 3mm Mucosal erythema alone did not qualify for the definition of erosions.

Study Protocol Detection & eradication of H pylori Randomization Follow-up End point

Detection & eradication of H pylori Two antral biopsy A history of upper GI bleeding or dyspepsia H pylori infection Triple therapy( PPI based ) for 7 d followed by PPI alone for 7 wks not eradicated received a 1-week course of triple therapy Eradicated  enrolled F/u endoscopy at 8 weeks eradicated,heald  enrolled Fail  excluded Unhealed ulcer/erosion PPI therapy for another 8 weeks

Detection & eradication of H pylori Two antral biopsy A history of upper GI bleeding or dyspepsia without H pylori infection, ulcer Unhealed ulcer/erosion PPI therapy for another 8 weeks Healed  enrolled PPI alone for 8 wks F/u endoscopy at 8 weeks Fail  excluded Healed  enrolled

Randomization Patients who satisfied all the following criteria  enrolled – Insignificant dyspeptic symptom limited to grade 0 or 1(Table 1) – Healed peptic ulcers/erosions – Absence of H pylori infection Aspirin 80 mg + famotidine 40 mg twice daily Aspirin 80 mg + pantoprazole 20 mg in the morning with a matching placebo in the evening randomization Follow up Table 1. Scroing system for dyspepsia Grade 0 Absent 1 Mild (easily tolerated) 2 Moderate (interfering with normal activities) 3 Severe(incapacitating; leaving the patient unable to perform normal activities)

Follow-up As outpatients every 16 weeks for 48 weeks Upper GI symptoms and Hb level –at every visit Recurrent dyspeptic symptoms ( > grade 2 ) despite antacid therapy  endoscopy Melena, hematemesis, severe epigastric pain (grade 3)  To visit the ED & endoscopy Otherwise, no scheduled endoscopy

End point The overall severity grading of dyspepsia –Tables 1 The definition of ulcer complications –Tables 2 The primary end point – The recurrence of dyspeptic or complicated ulcers/erosions. Table 1. Scroing system for dyspepsia grade 0 Absent 1 Mild (easily tolerated) 2 Moderate (interfering with normal activities) 3 Severe (incapacitating; leaving the patient unable to perform normal activities) Table 2. Prespecified criteria for Ulcer/Erosion Complications Upper Gl tract bleeding Hematemesis, melena with a nonmalignant ulcer or more than 10 erosions found on endoscopy or at surgery decrease of 2 g/dL in Hb level with a nonmalignant ulcer or more than 10 erosions found on endoscopy Gastric outlet obstruction Nausea and vomiting 24 hours after eating, with stenosis in the distal part of the stomach or duodenum, as a result of a nonmalignant ulcer found on endoscopy or at surgery Gastric or duodenal perforation Presence of perforation due to a nonmalignant ulcer that requires surgery

12 Fig 1. Progress of patients during the study Results

Table 4. Baseline Characteristics of the Patients Baseline demographic characteristics Clinical presentation (dyspepsia or bleeding) Severity of bleeding

Table 3. Premature Termination and Time to Occurrence

Famotidine ( n = 65 ) Pantoprazole ( n = 65 ) 13 pts (20%) None (0%)P< pts (12.3%) - significant dyspepsia without GI bleeding None (0%) P< pts (7.7%) - melena(2) - decrease in Hb(3) Primary end point

Table 5. Details of Patients With Recurrent Bleeding Ulcers/Erosions 16

CONCLUSION In patients with aspirin-related peptic ulcers/erosions high-dose famotidine therapy is inferior to pantoprazole in preventing recurrent dyspeptic or bleeding ulcers/erosions