Influence of risk factors on endoscopic and clinical ulcers in patients taking rofecoxib or ibuprofen in two randomized controlled trials

Background: Highly selective inhibitors of the inducible cyclooxygenase-2 e nzyme (coxibs) have been associated with less gastrotoxicity than nonselect ive NSAIDs in clinical studies. Aim: To evaluate the influence of risk factors for NSAID-induced gastrotoxi city on endoscopic and clinical ulcers in patients taking rofecoxib or ibup rofen. Methods: We analysed pooled data from two identical double-blind, randomize d, 12-week endoscopy studies which compared the gastroduodenal toxicity of placebo (n=371), rofecoxib 25 mg (n=390), rofecoxib 50 mg (n=379), and ibup rofen 2400 mg daily (n=376) in patients with osteoarthritis. The potential risk factors evaluated were: age (<65, <greater than or equal to>65 years), sex, race (white, nonwhite), Helicobacter pylori status, presence of gastr oduodenal erosions at baseline, a history of upper gastrointestinal disease , prior NSAID use within 30 days of study entry, and smoking. We also evalu ated these factors for possible association with the development of clinica lly-evident gastrointestinal perforations, ulcers or bleeds over 12 weeks. Results: Across all treatment groups, the likelihood of detecting endoscopi c ulcers, or of clinical presentation with a bleed, over 12 weeks was incre ased approximately 4-5-fold in patients with previous upper gastrointestina l disease (relative risk [95% confidence interval] of 4.2 [2.5, 7.1] for en doscopic ulcers; 3.8 [1.4, 10.6] for bleeds), or those with gastroduodenal erosions at baseline endoscopy (relative risk of 4.4 [2.6, 7.5] for endosco pic ulcers; 5.0 [1.9, 13.5] for bleeds). H. pylori infection did not increa se the risk of endoscopic ulcers or bleeds (relative risk of 1.1 [0.8, 1.6] for endoscopic ulcers; 0.3 [0.1, 0.9] for bleeds). The risk factor subgrou p effects were constant across all treatment groups, and the significantly higher incidence of ulcers with ibuprofen as compared to rofecoxib, and pla cebo was maintained in all risk factor subgroups. Conclusions: Gastroduodenal erosions at baseline and a clinical history of upper gastrointestinal disease, but not H. pylori colonization, increased t he risk for endoscopically-detected ulcers and clinical bleeds. Rofecoxib d id not magnify the risk in any of the patient subgroups studied.