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.
BACKGROUND
Studies that report prevention of ulcer recurrence among long-term users of nonsteroidal anti-inflammatory drugs (NSAIDs) that do not stratify for Helicobacter pylori status may not be generalizable to the large population of individuals without H pylori.


METHODS
This was a prospective, double-blind, multicenter, active- and placebo-controlled study among 537 patients without H pylori who were long-term users of NSAIDs and who had a history of endoscopically documented gastric ulcer. Patients were randomized to receive placebo, 200 microg of misoprostol 4 times a day, or 15 or 30 mg of lansoprazole once daily for 12 weeks. Ulcer status was determined by endoscopy at 4, 8, and 12 weeks.


RESULTS
Patients receiving lansoprazole (15 or 30 mg) remained free from gastric ulcer longer than those who received placebo (P<.001) but for a shorter time than those who received misoprostol. By week 12, the percentages of gastric ulcer-free patients were as follows: placebo, 51% (95% confidence interval [CI], 41.1%-61.3%); misoprostol, 93% (95% CI, 87.2%-97.9%); 15-mg lansoprazole, 80% (95% CI, 72.5%-87.3%); and 30-mg lansoprazole, 82% (95% CI, 75.0%-89.6%). A significantly higher proportion of patients in the misoprostol group reported treatment-related adverse events and early withdrawal from the study. When the impact of withdrawals on ulcer development was considered (as failures), therapy was successful for 69% for each of the active treatment groups and 35% for the placebo group.


CONCLUSIONS
Proton pump inhibitors such as lansoprazole are superior to placebo for the prevention of NSAID-induced gastric ulcers but not superior to misoprostol, 800 microg/d. When the poor compliance and potential adverse effects associated with misoprostol are considered, proton pump inhibitors and full-dose misoprostol are clinically equivalent.
Graham
David Y
DY
Veterans Affairs Medical Center (111D), 2002 Holcombe Blvd, Room 3A-320, Houston, TX 77030-4211, USA. dgraham@bcm.tmc.edu
Agrawal
Naurang M
NM
Campbell
Donald R
DR
Haber
Marian M
MM
Collis
Cyndy
C
Lukasik
Nancy L
NL
Huang
Bidan
B
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D064747:Lansoprazole; D008297:Male; D008875:Middle Aged; D016595:Misoprostol / Q000627:therapeutic use*; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011446:Prospective Studies; D054328:Proton Pump Inhibitors; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000188:drug therapy / Q000517:prevention & control*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D016595:Misoprostol; D064747:Lansoprazole; D009853:Omeprazole