Effects of Helicobacter pylori and Nonsteroidal Anti-Inflammatory Drugs on Peptic Ulcer Disease: A Systematic Review

Background & Aims: The aim was to systematically review the interactions between Helicobacter pylori (HP) infection and NSAID use on the risk of uncomplicated or bleeding peptic ulcer. Methods: All relevant full articles published in MEDLINE from January 1989-June 2004 were included. Sensitivity analyses for type of controls or use of aspirin or non-aspirin NSAIDs were performed. Results: In 21 studies involving 10,146 patients, uncomplicated peptic ulcer was more common in HP-positive than HP-negative patients (pooled odds ratio [OR], 2.17) or in HP-positive than HP-negative NSAID users (OR, 1.81). In 6 age-matched controlled studies, ulcer was more common in HP-positive than HP-negative patients (OR, 4.03), irrespective of NSAID use, and in NSAID users than non-users (OR, 3.10), irrespective of HP status; the risk of ulcer was 17.54-fold higher in HP-positive NSAID users than HP-negative non-users. The use of aspirin or non-aspirin NSAIDs did not affect the results. Ulcer bleeding was evaluated in 17 studies involving 4084 patients. NSAID use was more frequent in bleeding patients than control subjects (OR, 5.13), irrespective of HP status and type of controls. In contrast, HP infection in bleeding patients compared with control subjects was less frequent in the 8 studies with ulcer cases as control subjects (OR, 0.40) and more frequent in the 9 studies with uninvestigated subjects as controls (OR, 2.56). In the latter studies, presence compared with the absence of both HP and NSAIDs increased the risk of bleeding 20.83-fold. Conclusion: HP infection and NSAID use represent independent and synergistic risk factors for uncomplicated and bleeding peptic ulcer.