GASTROENTEROLOGY
LITERATURE ALERT!
LANDMARK ARTICLE - Required reading
Ulcer Prevention in Long-term Users of Nonsteroidal Anti-inflammatory Drugs Results of a Double-blind, Randomized, Multicenter, Active-and Placebo-Controlled Study of Misoprostol vs Lansoprazole David Y. Graham, MD; Naurang M. Agrawal, MD; Donald R. Campbell, MD; Marian M. Haber, MD; Cyndy Collis, BS; Nancy L. Lukasik, BSN; Bidan Huang, PhD
Although we commonly use PPI's to prevent NSAID ulcers, there is no FDA approval for its use. Only misoprostol has FDA approval for prevention of NSAID-associated ulcers. This article is particularly important, because it enrolled only patients with a prior history of endoscopically documented gastric ulcer in the past (with or without prior bleeding) and are now again taking full-dose NSAID therapy. All patients were H. pylori negative.
This article compares placebo to 200ug qid misoprostol (high dose) and to lansoprazole 30mg or 15mg once daily for 12 weeks. Patients were followed by monthly endoscopy, and all were H. pylori negative. Enrolled patients were taking a full dose of an NSAID (other than nabumetone or cardiac-dose aspirin) for at least1 month at enrollment and for the duration of the study
Main Findings
- While the misoprostol group had a greater reduction in the incidence of gastric ulcers than lansoprazole group (93% misoprostol vs 82% 30mg lansoprazole and 80% 15mg lansoprazole), many more people in the misoprostol group had to stop therapy due to side effects.
- If patients stopping therapy due to side effects in each group are considered failures, then the efficacy of misoprostol is equivalent to lansoprazole 15mg or 30 mg. Both were superior to placebo.
- Among patients on placebo, 49% had recurent gastric ulcers (defined as lesions >5 mm in diameter) at 12 weeks.
Take home message
- Misoprostol at a full dose of 200ug qid is superior to lasoprazole in preventing ulcer, but much less tolerated. In practice misoprostol and lansoprazole are equivalent when considering how many people do not take misoprostol due to side effects.
- Low dose lansoprazole was equal to 30 mg
- A 12 week study is not long enough to say that people with prior ulcers can take long-term NSAID's together with misoprostol or PPI and have no increased in severe ulcer-related morbidity.
- People with prior NSAID ulcers should definitely not take NSAID's without prophylaxis, and even with prophylaxis, ulcer-related complications may still occur.
