Famotidine did not reduce mortality or morbidity associated with bleeding peptic ulcers
ACP J Club. 1993 Mar-April;118:45. doi:10.7326/ACPJC-1993-118-2-045
Walt RP, Cottrell J, Mann SG,Freemantle NP, Langman MJ. Continuous intravenous famotidine for haemorrhage from peptic ulcer. Lancet. 1992 Oct 31;340:1058-62.
To study if famotidine, used in conjunction with usual care, will reduce mortality and morbidity from bleeding peptic ulcers.
Randomized, double-blind, placebo-controlled trial with follow-up to hospital discharge.
67 hospitals in the United Kingdom and Ireland.
1005 patients (mean age 63 y, 44% < 65 y, 63% men) hospitalized with upper gastrointestinal bleeding from duodenal or gastric ulcers. 44.5% had gastric ulcers, 54.5% had duodenal ulcers, and 1% had both. Endoscopies were done within 24 hours of admission to confirm ulcers and recent hemorrhage (oozing, red blood clot, visible vessels, or black slough). Follow-up was complete.
All patients had usual care given at the discretion of the medical staff. 497 patients received a single 10-mg intravenous bolus of famotidine, followed by continuous infusion of 3.2 mg/h for 72 hours. Oral famotidine, 40 mg, was then given at night. Matching placebo was given to 508 patients.
Main outcome measures
Charts were abstracted for mortality, rebleeding (decreased hemoglobin, fresh hematemesis, or hypotension after initial resuscitation), and surgery (done when bleeding or rebleeding did not stabilize). Autopsy reports and death certificates provided causes of death.
The study was designed to detect a 10% difference in survival at the P = 0.01 level with interim analysis after 500 patients. The groups did not differ for mortality (31 deaths in the famotidine group vs 25 in the placebo group), rebleeding (119 vs 125 patients), surgery (77 vs 86 patients), duration of hospital stay (7 vs 8 days), mean transfusion requirements (3 vs 4 units of blood), possibly drug-related (2.6% vs 1.8%) or serious adverse reactions (0.9% vs 0.8%), or withdrawals because of adverse reactions (5.8% vs 3.1%).
Using a logistic regression analysis, the relative risk for mortality for age > 65 years was 8.6 (95% CI 3.3 to 22.4) and for blood pressure < 100 mm Hg was 3.0 (CI 1.6 to 5.6). No treatment-associated differences were found using logistic regression analysis.
Famotidine, used in addition to usual care, did not decrease mortality or morbidity associated with bleeding from peptic ulcers in hospitalized patients.
Source of funding: Merck Sharp and Dohme Research Laboratories.
For article reprint: Dr. R.P. Walt, Department of Medicine, Queen Elizabeth Hospital, Birmingham B15 2TH, England, UK. FAX 44-21-627-2202.
Despite the lack of convincing evidence showing their efficacy, antisecretory drugs are widely used for the management of peptic ulcer bleeding. Although the rationale for therapy is unquestioned, this large, well-designed, multicenter trial has clearly shown that antisecretory therapy for bleeding peptic ulcers is inadequate.
Recent work by Walt and colleagues (1) has shown that omeprazole, the H+-K+ ATPase inhibitor, failed to improve the outcome of patients with upper gastrointestinal tract bleeding lesions (1). Both studies used effective therapy, proven to neutralize intragastric acidity. Previous uncertainty about the efficacy of H2-receptor antagonists was based on incomplete acid suppression with bolus therapy. This study used a bolus intravenous injection followed by continuous infusion ("primed infusion") to maintain elevated intragastric pH. This study, like the omeprazole trial, has shown that antisecretory therapy alone cannot decrease rebleeding or ulcer mortality.
Endoscopic findings have important prognostic significance. The presence of a visible vessel in the ulcer base predicts rebleeding in up to 50% of patients (2). This study was initiated at the dawn of therapy of interventional endoscopy for bleeding ulcers. Visible vessels were found in 20% of the patients, a subgroup in whom there was a clear consensus about the efficacy of endoscopic therapy (3).
The failure of antisecretory therapy confirms that endoscopic evaluation of the bleeding lesion is essential for assessing rebleeding risk and also, if necessary, for therapy. Despite its lack of efficacy as primary therapy, pharmacologic therapy to control pH is important for ulcer healing, is extremely safe, and should now be viewed as an adjunct to endoscopic therapy.
James Scheiman, MD
The University of Michigan Medical CenterAnn Arbor, Michigan, USA