Proton-pump Antagonists May be Effective Therapy
4-9 A COMPARISON OF OMEPRAZOLE AND PLACEBO FOR BLEEDING PEPTIC ULCER
The function of platelets is severely impaired at low pH. Pepsin can digest blood clots overlying ulcer craters; its activity is pH-related. Thus adjusting gastric pH toward neutrality could stabilize a clot over an ulcer and stop bleeding or prevent a recurrence.
Trials of histamine H2-receptor antagonists in patients with bleeding peptic ulcers have not demonstrated a significant benefit.
This trial assessed the potential benefit of the proton-pump antagonist omeprazole [Prilosec] in treatment of bleeding peptic ulcer.
Conclusion: Omeprazole decreased the rate of further bleeding and the need for surgery in some subsets of patients.

STUDY

1. Double-blind, placebo-controlled trial of 220 patients compared omeprazole with placebo.
2. Patients had duodenal, gastric, and stomal ulcers and signs of recent bleeding, confirmed by endoscopy. In 26 patients there was arterial spurting; in 34, active oozing; in 35, non-bleeding visible ulcers; in 125, adherent clots.
3. Randomized to 1) oral omeprazole 40 mg every 12h for 5 days (a high dose), or 2) placebo.
4. Both groups were allowed to receive a liquid antacid.

RESULTS

1. Eleven percent of those receiving omeprazole had continued bleeding, or further bleeding, vs 36% of those receiving placebo. (NNT=4).
2. Eight patients in the omeprazole group and 26 in the placebo group required surgery to control bleeding.
3. Deaths: Two in omeprazole group vs 6 in the placebo group.
4. Transfusions: 29% in the omeprazole group vs 71% in the placebo group.
5. Those in the subgroup with active arterial spurting or oozing did not benefit from omeprazole. Those with non-bleeding visible vessels or adherent clots benefited.
6. A hemoglobin concentration of 10.6 per deciliter or less, a systolic of 100 mg Hg or less on admission, and an ulcer size or 1 cm or larger were associated with an increased rate of further bleeding.

DISCUSSION

1. "We found that omeprazole therapy was associated with significant reductions in the rates of further bleeding and surgical intervention, the number of days in the hospital, and the need for transfusion."
2. The benefit was limited to patients with non-bleeding visible vessels and adherent clots. Those with arterial spurting and oozing did not benefit. Endoscopic therapy, if available, should be instituted at the beginning of treatment in patients with arterial spurting. (This latter group responds favorably to endoscopic treatment.) Surgery should be considered only if this treatment fails.
3. Mortality from bleeding peptic ulcers has remained constant at 5%-10% over the past 6 decades, possible due to an increasing proportion of elderly patients with comorbid illnesses.
4. "Our findings support the use of potent acid suppression with high doses of proton-pump inhibitors in patients with bleeding peptic ulcers."

CONCLUSION
In patients with bleeding peptic ulcers and signs of recent bleeding, treatment with omeprazole decreased the rate of further bleeding and the need for surgery.
NEJM April 10, 1997; 336: 1054-58 Original investigation from Sheri Kasmir Institute of Medical Sciences, Kashmir, India

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