Certain Drugs Fail To Protect Stomach From NSAID Side Effects

By Cameron Johnston
Special to DG News

VANCOUVER, BC -- Sept. 1, 1999 -- The results of a meta-analysis presented at the Gastro '99 -- the Pan-American Congress on Digestive Diseases conference show little evidence that H2 receptor antagonists or proton pump inhibitors are effective in reducing damage to the gastric lining caused by non-steroidal anti-inflammatory (NSAID) use.

The analysis looked at the results of 26 studies comprising more than 19,300 patients who had arthritis and were treated with NSAIDs. Gastric complications including bleeding, hospitalisation, gastric perforation and, in some cases, death are all well-known side effects of NSAID use. For many years it has been common practice to treat patients who develop what is referred to as NSAID gut-rot with H2-receptor antagonists, sucralfate and, most recently, with proton pump inhibitors.

Misoprostol is marketed by Searle as Cytotec and as Arthrotec (in combination with diclofenac sodium).

The most common proton pump inhibitors are AstraZeneca’s Losec (omeprazole) and Solvay’s Pantoloc (pantoprazole). Common H2 receptor antagonists include SmithKline Beecham’s Tagamet (cimetidine), Lilly’s Axid (nizatidine) and Glaxo Wellcome’s Zantac (rantitidine)

Adding misoprostol and other agents to NSAIDs was intended not so much to reduce acid secretion but to reinforce the protective lining of the stomach which is suppressed by one of the components in the NSAID.
However, results of the study, which was conducted by researchers at McMaster University in Hamilton,ON., and in Boston, MA., report that significant reductions in the number of ulcers was reported only in the group who received misoprostol (odds ratio 0.31 CI [0.25-0.39]).

Those who took H2 receptor antagonists, another common preventive for ulcer disease, had an odds ratio of 0.51 (CI 0.51-0.91). Data were insufficient for proton pump and sucralfate studies.

Similarly, the incidence of gastric bleeding was reduced by one-third in patients taking misoprostol, whereas data was insufficient to say whether those taking H2 receptor antagonists or using PPIs saw the same benefit.

However, a second meta-analysis conducted by doctors at Memorial University in St John’s, Newfoundland, reports that there was a significant advantage to using proton pump inhibitors over either placebo or H2 receptor antagonists in patients with peptic ulcer disease. The second meta-analysis showed an odds ratio for re-bleeding of 0.56, meaning the patients who used PPIs were only half as likely to have a re-bleeding episode as those who were using the other two therapies.

The researchers note, however, that there was a significant increase in the risk of mortality when the patients were receiving intravenous PPIs. PPIs represent a significant improvement over H2 receptor antagonists or placebo, but further investigation is needed to determine whether they are truly safe in view of the increased risk of mortality, they reported.

The issue of when or whether one drug or series of drugs is more effective than another is clouded somewhat by the issue of how a gastric lesion is defined. If, for example, a lesion of 5 mm in diameter is used as a cut-off point, the number of patients who are considered to have true ulcers will be 40 per cent lower than if doctors use a 3 mm lesion as the cut-off point.