OMEPRAZOLE AMELIORATES ASPIRIN-INDUCED GASTRODUODENAL INJURY

Aspirin and nonsteroidal antiinflammatory drugs (NSAIDs) damage the gastroduodenal epithelium by two mechanisms: direct toxic effects and effects related to the depletion of endogenous prostaglandins. The prostaglandin-depleted mucosa has increased susceptibility to luminal aggressive factors, yet the role of acid in the pathogenesis of the NSAID ulcer is controversial. In humans, standard doses of H-2-receptor antagonists prevent only duodenal injury and provide no protection for the gastric mucosa. It is not known whether more potent suppression of acid can prevent NSAID damage. Twenty healthy volunteers were randomized to a double-blind, placebo-controlled, crossover study to determine if omeprazole, 40 mg/day prevents gastroduodenal injury due to two weeks of aspirin administration (650 mg four times a day). The severity of mucosal injury was quantitated by endoscopy and stratified by a scale from 0 (normal) to 4 (ulcer). Fourteen of the 20 subjects had less gastric injury during cotherapy with omeprazole. All six with no difference received aspirin plus omeprazole in the first treatment period. Omeprazole significantly decreased aspirin-induced gastric mucosal injury (P < 0.001, Wilcoxon signed-rank test). Omeprazole protected 85% of subjects from extensive gastric erosions (often associated with evidence of intraluminal bleeding or ulceration, whereas 70% of the subjects developed aspirin-induced grades 3 and 4 gastric injury on placebo (P < 0. 01 by X(2)). No subject taking omeprazole developed duodenal injury of any grade, while 50% taking placebo developed erosions and 15% had ulcer (P < 0.001). Medication side effects were mild in the majority of subjects. Heartburn occurred in seven subjects on aspirin and placebo vs one on aspirin and omeprazole (P < 0.01). Salicylate levels were 7.39 +/- 4.72 mg/dl (535 +/- 340 mu mol/liter) in the placebo group and 6.95 +/- 4.3 mg/dl (503 +/- 311 mu mol/liter) in the omeprazole group. We conclude that omeprazole, 40 mg/day eliminates duodenal injury and markedly ameliorates gastric injury due to administration of aspirin 2600 mg/day. Omeprazole prophylaxis of NSAID injury deserves further study.