Ulcer recurrence in high-risk patients receiving nonsteroidalanti-inflammatory drugs plus low-dose aspirin: results of a post HOC subanalysis.

BACKGROUND: Concomitant aspirin use is a risk factor for nonsteroidal anti-inflammatory drug (NSAID)-associated upper gastrointestinal toxicity. In high-risk individuals, such as those with a history of NSAID-related gastric ulcer bleeding, gastroprotective therapy with a proton pump inhibitor has been reported to reduce the risk of recurrent aspirin-associated gastroduodenal ulcer bleeding.

OBJECTIVE: This analysis compared the efficacy of misoprostol, lansoprazole, and placebo in reducing the risk of gastric or duodenal ulcer recurrence in patients taking NSAIDs and low-dose aspirin.

METHODS: This post hoc subanalysis was based on a previous multicenter, prospective, randomized, double-blind, placebo-controlled, 12-week study in patients who had a history of gastric ulcer, were Helicobacter pylori negative, required chronic NSAID therapy, and were free of gastric or duodenal ulcer on baseline endoscopy. The study treatments were misoprostol 200 microg QID or lansoprazole 15 or 30 mg OD. The subanalysis included data from patients in the intent-to-treat cohort who took aspirin at an amount <or=325 mg/d. The end point was the cumulative rate of gastric ulcers, as assessed by serial endoscopy at 4, 8, and 12 weeks.

RESULTS: Of 535 intent-to-treat patients from the primary study, 70 (40 men, 30 women; mean [SD] age, 64.7 [10.0] years; age range, 40-83 years) met the criteria for inclusion in the subanalysis. The proportions of patients who were free of gastric ulcers at the end of 12 weeks were 96% in the misoprostol group, 93% in the lansoprazole 15-mg group, 100% in the lansoprazole 30-mg group, and 35% in the placebo group (P <or= 0.008, each active treatment vs placebo). Adverse events considered possibly or probably related to treatment occurred in 5 (20.0%) misoprostol recipients (4 episodes of diarrhea, 1 episode of abdominal pain), 1 (14.3%) recipient of lansoprazole 30 mg (1 episode of pharyngitis), and 3 (13.6%) placebo recipients (1 episode each of abdominal pain, palpitations, and dyspepsia).

CONCLUSIONS: In this subgroup analysis in patients at high risk for recurrence of gastric ulcer, use of cotherapy with misoprostol 200 microg QID or lansoprazole 15 or 30 mg OD significantly lowered the risk for gastric ulcer recurrence.