Influence of sex and Helicobacter pylori on development and healing of gastroduodenal lesions in non-steroidal anti-inflammatory drug users

Abstract

Background and aims: Factors predisposing to endoscopic ulcer formation or healing with non-steroidal anti-inflammatory drugs (NSAIDs) have not been well defined.

Methods: We used multivariate analysis of data from three large similar trials to identify factors associated with endoscopic lesions and healing. We compared the effectiveness of omeprazole 20 mg and 40 mg daily, misoprostol 200 micro g four times daily, and ranitidine 150 mg twice daily in healing ulcers and erosions at different sites and in patients who were Helicobacter pylori positive and negative.

Results: Older age, past ulcer history, rheumatoid arthritis, and H pylori infection were significantly associated with ulcers. Duodenal ulcer was significantly more likely than gastric ulcer with a past ulcer history (odds ratio 1.59, 1.16-2.17), H pylori infection (1.4, 1.04-1.92), and male sex (2.35, 1.75-3.16) while female sex, older age (> or = 60 years: 1.39, 1.03-1.88), and higher NSAID dose (>1 defined daily dose: 1.57, 1.16-2.14) were associated with gastric ulceration. Sex differences were seen in both H pylori positive and negative patients. Gastric and duodenal ulcer healing was significantly faster with omeprazole 20 mg than with misoprostol 200 micro g four times daily or ranitidine 150 mg twice daily although misoprostol was more effective at healing erosions. Gastric ulcer healing was slower with large ulcers (0.37, 0.25-0.54 for >10 mm v 5-10 mm) or a past ulcer history (0.51, 0.34-0.76), and faster with H pylori infection (1.55, 1.06-2.29), especially with acid suppression (72% v 37% at four weeks with ranitidine).

Conclusions: Among NSAID users, H pylori and male sex independently increase the likelihood of duodenal ulceration. H pylori infection does not affect duodenal ulcer healing and enhances gastric ulcer healing by ranitidine and possibly other acid suppressing treatments.

Figure 1

Outline of the trials that acted as the source of patients for analysis. Endoscopy positive is defined as an ulcer or more than 10 erosions present in either the stomach or duodenum. OPPULENT patients were enrolled from centres participating in the OMNIUM study. However, not all OMNIUM participants also participated in the OPPULENT study.

Figure 2

(A) Endoscopic diagnoses in individual patient populations contributing to those analysed. All patients in the OMNIUM and ASTRONAUT centres that did not participate in the OPPULENT study. (B) All patients in the OMNIUM centres who also enrolled patients into the OPPULENT study. (C) All patients enrolled into the OPPULENT study. Cohort 1 is all patients in the OMNIUM and ASTRONAUT studies. Cohort 2 is all patients recruited into either the OMNIUM or OPPULENT studies in dual participation centres.

Figure 3

Effect of potential risk factors on endoscopic findings. Influences are expressed as odds ratios with 95% confidence intervals. Data concerning any clinically significant lesions versus none (A) are from cohort 2. Data concerning ulcer versus erosions (B) and gastric ulcer (GU) versus duodenal ulcer (DU) (C) are from cohort 1. Except where indicated, comparison is with all patients without the stated risk factor. RA, rheumatoid arthritis; OA, osteoarthritis; PH PU, past history of peptic ulcer; NSAID, non-steroidal anti-inflammatory drug; DDD, defined daily dose.

Figure 4

Effect of potential influences on treatment success or ulcer healing over eight weeks. Except where indicated, comparison is with all patients without the stated risk factor. GE, gastric erosions; GU, gastric ulcer; DU, duodenal ulcer; PH, past history; NSAID, non-steroidal anti-inflammatory drug; DDD, defined daily dose; RA, rheumatoid arthritis; OA, osteoarthritis; Om 20, omeprazole 20 mg; Om 40, omeprazole 40 mg; Miso, misoprostol 200 μg four times daily; Ran, ranitidine 150 mg twice daily.

Figure 5

Healing of individual lesions by Helicobacter pylori status. O20, omeprazole 20 mg daily; O40, omeprazole 40 mg daily; Miso, misoprostol 200 μg four times daily; Ran, ranitidine 150 mg twice daily. (Note the Y axis starts at 40%.)