H. pylori infection plus NSAID use synergistically increases peptic ulcer risk

By Karla Gale

NEW YORK (Reuters Health) – A synergistic interaction between the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori infection increases the risk of peptic ulcer and bleeding ulcer above and beyond that contributed by either factor alone.

These findings, reported in The Lancet for January 5, are accompanied by a second report substantiating the value of screening for and treatment of H. pylori infection among patients starting long-term NSAID therapy.

Through a search of the literature between 1984 and 2000, Dr. Richard H. Hunt, and associates at McMaster University Medical Center in Hamilton, Ontario, Canada, identified 25 studies on the prevalence of peptic-ulcer disease in users of NSAIDs in the presence or absence of H. pylori infection.

In 16 studies involving 1625 patients, the summary odds ratio for peptic ulcer disease was 2.12 for H. pylori-positive NSAID users compared with H. pylori-negative NSAID users.

For NSAID users without H. pylori infection, the odds ratio for peptic ulcer disease was 19.4 compared with control subjects.

When NSAID users infected with H. pylori were compared with uninfected control subjects, the risk of peptic ulcer disease increased to 61.1.

"Compared to controls, when an individual has the infection and is taking the drug, the risk is enormous," Dr. Hunt commented to Reuters Health.

Dr. Hunt's group also found that in nine case-control studies involving 893 patients with bleeding peptic ulcer and 1002 control subjects, the odds ratio for developing ulcer bleeding associated with H. pylori infection was 1.79, and for NSAID use alone was 4.85. For the two risk factors combined, the result was additive, with a combined risk of 6.13.

In the second paper, Dr. Francis K. L. Chan, of Prince of Wales Hospital in Hong Kong, and colleagues demonstrate that the risk of ulcers in these patients can be significantly reduced by using a urea breath test to screen for H. pylori infections before NSAID treatment is started.

In their 6-month trial involving arthritis patients with H. pylori infection, 51 patients were randomly assigned to eradication treatment and 49 to placebo treatment. Eradication therapy comprised amoxicillin 1 g, clarithromycin 500 mg and omeprazole 20 mg, each given b.i.d. for 1 week. Control subjects were treated with omeprazole 20 mg plus placebo b.i.d. for 1 week. All subjects received diclofenac slow release 100 mg q.d. for 6 months.

During follow-up, endoscopy showed that five patients in the eradication group developed nonbleeding ulcers. In the placebo group, 15 patients had ulcers, including 3 that began bleeding and required treatment in an emergency department.

"Our results suggest that screening and treatment of H. pylori infection for patients starting long-term NSAID therapy has the potential to reduce the ulcer risk…[and may allow reservation of] the use of expensive anti-ulcer drugs or cyclo-oxygenase-2-selective-NSAIDs for patients at very high risk," Dr. Chan's group writes.

"I don't think people in the medical community will be surprised by these results, but many will be pleased to see a rather crazy hypothesis that has been flying around, that the infection may actually protect from NSAID injury, has been effectively nailed," Dr. Hunt said, "both in our retrospective meta-analysis and in the prospective study Francis Chan et al."

Regarding the findings of Dr. Chan's group, Dr. Hunter said that treating H. pylori infection "is not a way to avoid the use of a COX-2 inhibitor or a conventional NSAID plus a proton pump inhibitor in those people who have a previous history of ulcer."

In a commentary, Dr. Roy E. Pounder, of the Royal Free and University College Medical School in London, notes that NSAID users remain at increased risk of ulcers even in the absence of H. pylori infection. One suggestion he makes is to include potent anti-acid-secretory medication to the NSAID regimen.

He adds, "Perhaps patients should start on a COX-II inhibitor, if cost and safety issues are resolved, with a more leisurely eradication of H. pylori if found to be positive."

Lancet 2002;359:3-4,9-22.

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