1. Nonsteroidal anti-inflammatory drug gastropathy
Christopher J. Hawkey 
Gastroenterology 
Volume 119, Issue 2, Pages (August 2000)
DOI: /gast
Copyright © 2000 American Gastroenterological Association Terms and Conditions

2. Fig. 1
(A) Mechanisms underlying mucosal defense. Mucosal blood flow is of particular importance and influences bicarbonate secretion. In many instances, enteric neuronal reflexes and NO have been shown to activate the same mechanisms as prostaglandins. (B) Mechanisms of ulcer healing. Growth factors promote epithelial cell migration and proliferation. During remodeling of granulation, tissue inflammatory cells are replaced by fibroblasts and microvessels. (Reprinted with permission from Am J Physiol 1995;268:G276–G285. Copyright 1995, the American Psychiatric Association.)
Gastroenterology  , DOI: ( /gast )
Copyright © 2000 American Gastroenterological Association Terms and Conditions

3. Fig. 2
Interactions between NSAIDs and age or past history, leading to enhanced risks when both risk factors are present. Odds ratios and 95% confidence intervals are shown. (Data from Garcia Rodriguez and Jick.60)
Gastroenterology  , DOI: ( /gast )
Copyright © 2000 American Gastroenterological Association Terms and Conditions

4. Fig. 3
Dose relationship of therapeutic and toxic effects of NSAIDs. (A) Dose-dependent pain relief in osteoarthritis with naproxen. (Reprinted with permission.76) (B) Effect of increasing dose on risks of ulcer complications. (Data from Ann Intern Med 1991;114:257 and Garcia Rodriguez and Jick.60)
Gastroenterology  , DOI: ( /gast )
Copyright © 2000 American Gastroenterological Association Terms and Conditions

5. Fig. 4
Relative risk of ulcer complication with individual NSAIDs compared with ibuprofen. Data show results of meta-analysis involving 12 trials. Ibuprofen ≤1200 mg daily was associated with a risk of approximately 2. This shows the extent to which risks are higher than with other NSAIDs. Risks also increase in a dose-dependent fashion. (Reprinted with permission.63)
Gastroenterology  , DOI: ( /gast )
Copyright © 2000 American Gastroenterological Association Terms and Conditions

6. Fig. 5
Epidemiologic studies investigating interaction between H. pylori and NSAIDs. (A) Studies that reported risks in NSAIDs users according to H. pylori status compared with patients with neither risk factor. Odds ratios for presentation with an ulcer complication (usually bleeding) with 95% confidence intervals are shown for NSAID users with and without evidence of H. pylori infection, compared with matched controls. (B) Studies reporting the extent of risk modification by H. pylori. The effect of H. pylori on risk of NSAID-associated ulcer complications is shown as odds ratios and 95% confidence intervals for NSAID users infected with H. pylori compared with NSAIDs users not infected with H. pylori. Two studies report data in both ways. (Data from Cullen et al.79 and Stack et al.44) Patient populations vary. For example, Stack et al. report data for aspirin and nonaspirin NSAIDs (shown here) separately, whereas in the data of Aalykke et al., aspirin and nonaspirin users are integrated.
Gastroenterology  , DOI: ( /gast )
Copyright © 2000 American Gastroenterological Association Terms and Conditions

7. Fig. 6
Important differences between COX-1 and COX-2. See text for details. Phe, phenylalanine; Leu, leucine; Iso, isoleucine; Val, valine; Arg, arginine. The COX-1–binding site for nonselective NSAIDs is at arginine 120, which is also present in COX-2. (Adapted with permission from Hawkey CJ. COX-2 inhibitors. Lancet 1999;353:307–314. © by The Lancet Ltd.)
Gastroenterology  , DOI: ( /gast )
Copyright © 2000 American Gastroenterological Association Terms and Conditions

8. Fig. 7
Cumulative ulcer incidence with placebo, ibuprofen, and rofecoxib (25 and 50 mg). Combined data of 2 studies that enrolled 1516 patients. Scheduled endoscopies were at 6, 12, and 24 weeks. Patients receiving placebo left the study at 16 weeks. Twelve-week ulcer rates on 25 mg rofecoxib met prespecified criteria for equivalence to placebo. Rates with 50 mg rofecoxib were not significantly different from placebo. Rates with rofecoxib were significantly different from ibuprofen. Similar reductions compared with nonselective NSAIDs have been reported with celecoxib.109 (Reprinted with permission.67)
Gastroenterology  , DOI: ( /gast )
Copyright © 2000 American Gastroenterological Association Terms and Conditions

9. Fig. 8
Prevention of gastric and duodenal ulcer by H2 antagonists and misoprostol. Meta-analysis of studies of ≥3 months' duration up to Left panel shows odds ratio for ulcer development, with 95% confidence intervals. Right panel shows rate differences with 95% confidence intervals. (Data from Hawkey et al.66)
Gastroenterology  , DOI: ( /gast )
Copyright © 2000 American Gastroenterological Association Terms and Conditions

10. Fig. 9
Studies comparing omeprazole with (A) misoprostol (OMNIUM study) or (B) ranitidine (ASTRONAUT study) in healing of gastric ulcers, duodenal ulcers, and gastroduodenal (principally gastric) erosions. See text for details. (Reprinted with permission.66 Copyright © 1998 Massachusetts Medical Society. All rights reserved.)
Gastroenterology  , DOI: ( /gast )
Copyright © 2000 American Gastroenterological Association Terms and Conditions

11. Fig. 10
Comparison of omeprazole (20 mg) with misoprosol (200 μg twice daily) (OMNIUM study), ranitidine (150 mg twice daily) (ASTRONAUT study), or placebo (SCUR and OPPULENT studies) in prevention of NSAID-associated upper gastrointestinal problems. Endpoint for ASTRONAUT and OMNIUM was development of a gastric or a duodenal ulcer, or >10 erosions at either site or moderate or severe dyspepsia. Endpoint for SCUR and OPPULENT studies was development of an ulcer. Annotations show the proportion of patients not reaching an endpoint over 6 months. (Reprinted with permission from Olbe L, ed. Proton pump inhibitors. Basel: Birkhauser Verlag, 1999; 193–204.)
Gastroenterology  , DOI: ( /gast )
Copyright © 2000 American Gastroenterological Association Terms and Conditions