The heartburn drugs Prilosec and Prevacid reduce the risk of bleeding, abdominal surgery and death when used to treat life-threatening peptic ulcers, according to an updated systematic review of data.

Use of the potent acid-suppressing drugs, called proton pump inhibitors, “provides the greatest benefit to those patients at the greatest risk of serious outcomes,” the review says.

Although the review found no evidence that PPI treatment improves survival of patients with less serious ulcers, reductions in re-bleeding and surgery held true.

“The results of this meta-analysis strongly suggest that PPIs should be administered to patients with endoscopically-documented peptic ulcer bleeding,” conclude review authors led by Grigoris Leontiadis, M.D., a Greek gastroenterologist.

A peptic ulcer is a sore in the lining of the stomach or small intestine. Ten percent of Americans have them during their lifetime, according to the U.S. Centers for Disease Control and Prevention.

Peptic ulcers can be life-threatening if they progress to the point of hemorrhage or perforation. Emergency treatment may include fluid replacement, blood transfusions and injections or cauterization through an endoscope.

“Adequate resuscitation of the patient and endoscopic treatment of the high-risk ulcer continue to be the most important points of management,” said review coauthor Colin Howden, M.D., a gastroenterologist at Northwestern University in Chicago. “PPI therapy appears to be beneficial over and above that.”

The review appears in the most recent issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

The updated review includes pooled data from 24 randomized controlled trials that included nearly 4,400 participants with bleeding peptic ulcers. The trials compared three oral and/or intravenous PPIs - omeprazole, pantoprazole and lansoprazole - to either no drug treatment or alternative acid-suppressing drugs known as H2 receptor antagonists, such as Zantac and Tagamet.

Combined data from all the studies showed re-bleeding rates of 10.6 percent for PPIs compared with 17.3 percent for other or no treatment. Surgical rate was 6.1 percent for PPIs compared with 9.3 percent for other or no treatments combined; however, the reduction in surgery rate was not significant when comparing PPIs with H2 receptor antagonists alone. For patients with active bleeding, PPIs significantly reduced mortality.

PPIs are currently approved in the United States for treatment of acid reflux disease and uncomplicated ulcers but not for bleeding ulcers. In the past few years, however, most American specialists have followed the lead of European and Asian doctors who routinely administer PPIs along with other treatments for bleeding ulcers, says Howden. This “off-label” use is likely to continue as U.S. drug manufacturers are not currently pursuing further government approval of these medications.

Only one study took place in the United States, while 15 trials included predominantly European patients and eight trials focused on Asians. The review found greater benefits of PPI in the Asian studies than in those conducted elsewhere.

Possible explanations include better overall health of Asian patients, longer treatment times, or more effective inhibition of stomach acid in Asians than Europeans.

None of the trials compared different PPIs head-to-head, so it remains unknown if any one is more effective than the others. It was also impossible to determine whether oral or intravenous delivery had greater benefits.

Resolving questions about delivery, dosage and timing of PPI therapy for ulcers is difficult without approval of the drugs for this use. “We have to extrapolate from those [Asian] studies, bearing in mind that our patients might make more acid and might need better suppression,” said David Metz, M.D., a gastroenterologist at the University of Pennsylvania Health System.

For European-American patients with low-risk ulcers, Metz believes that oral PPI therapy is adequate. For those with severe bleeding, however, he advocates a PPI injection followed by a continuous intravenous drip for 24 to 48 hours.

“There’s no reason in my opinion not to give bigger doses. The harm is minimal if anything, and the benefit is potentially more,” Metz said. Drug costs are small compared to the cost of major abdominal surgery, he said.

Howden has been a paid consultant and received research support and/or speaking honoraria from more than a dozen pharmaceutical companies. Coauthor Dr. V.K. Sharma has also received honoraria and research support from several pharmaceutical companies.

Leontiadis GI, Sharma VK, Howden CW. Proton pump inhibitor for acute peptic ulcer bleeding. The Cochrane Database of Systematic Reviews 2006, Issue 1.

http://www.cochrane.org