Gastroenterology

Gastroenterology

Volume 123, Issue 4, October 2002, Pages 1006-1012
Gastroenterology

Clinical–Alimentary Tract
Stratifying the risk of NSAID-related upper gastrointestinal clinical events: Results of a double-blind outcomes study in patients with rheumatoid arthritis,☆☆

https://doi.org/10.1053/gast.2002.36013Get rights and content

Abstract

Background & Aims: Epidemiologic data indicate that the risk of nonsteroidal anti-inflammatory drug (NSAID)–related gastrointestinal (GI) clinical events varies based on patients' clinical characteristics. The authors determined risk factors for NSAID-related clinical upper GI events and the event rates, absolute risk reductions, and numbers needed to treat for individual risk factors for a nonselective NSAID and a selective cyclooxygenase 2 inhibitor in a double-blind outcomes trial. Methods: Eight thousand seventy-six rheumatoid arthritis patients aged ≥50 years (or ≥40 on corticosteroid therapy) were randomly assigned to rofecoxib 50 mg daily or naproxen 500 mg twice daily for a median of 9 months. The development of clinical upper GI events (bleeding, perforation, obstruction, and symptomatic ulcer identified on clinically indicated work-up) was assessed. Results: Significant risk factors included prior upper GI events, age ≥65, and severe rheumatoid arthritis (RR, 2.3–3.9). Patients administered naproxen who had prior upper GI complications or who were aged ≥75 years had 18.84 or 14.46 events per 100 patient-years, and the risk of events remained constant over time. The reduction in events with rofecoxib was similar in high- and low-risk subgroups (RR, 0.31–0.68). The number needed to treat with rofecoxib instead of naproxen to avert 1 GI event was 10–12 in highest risk patients (prior event, age ≥75 years, or severe rheumatoid arthritis), 17–33 in patients with other risk factors, and 42–106 in low-risk patients. Conclusions: NSAID-related GI events increase dramatically with risk factors such as prior events or older age. Ten to twelve high-risk patients need to be treated with a protective strategy such as the selective cyclooxygenase 2 inhibitor, rofecoxib, to avert a clinical GI event.

GASTROENTEROLOGY 2002;123:1006-1012

Section snippets

Materials and methods

Rheumatoid arthritis patients aged ≥50 years (or ≥40 years and receiving corticosteroid therapy) and who were expected to require NSAIDs for ≥ 1 year were eligible. Exclusion criteria included use of aspirin or other antiplatelet agents, anticoagulants, misoprostol, sucralfate, proton pump inhibitors, or prescription-strength histamine2-receptor antagonists (lower over-the-counter doses were allowed: cimetidine 400 mg daily, ranitidine 150 mg daily, famotidine 20 mg daily, nizatidine 150 mg

Results

The 8076 patients enrolled were followed up for a median of 9 months (range, 0.5–13 months). Baseline characteristics in the 2 study groups were similar3: 97% met American College of Rheumatology criteria for rheumatoid arthritis, 26% were aged ≥65 years, 56% took corticosteroids at entry, 83% took disease-modifying agents, 42% were seropositive for Helicobacter pylori, and 8% had a history of clinical upper GI events. There were 177 confirmed upper GI clinical events and 53 confirmed

Discussion

This large, prospective, double-blind GI outcomes trial in patients with rheumatoid arthritis identified prior upper GI clinical events, age older than 65 years, and severe disability caused by rheumatoid arthritis as important risk factors for developing upper GI events, with approximately 2- to 4-fold increases in risk for each individual factor. In patients taking the nonselective NSAID naproxen, the annualized incidence of clinically significant upper GI events was more than 14% in patients

Acknowledgements

Dr. Laine is a consultant or has received research support from Merck, Pharmacia, and Pfizer. Dr. Hawkey has received research funding from AstraZeneca, Alizyme, Boehringer Ingelheim, Boots Healthcare, Glaxo Wellcome, Merck, Merckle, NicOx, Novartis, Parke Davis, Pfizer/Pharmacia, Searle, SmithKline Beecham, and Wyeth Lederle. Dr. Bombardier is a consultant for Merck Research Laboratories, Schering Canada, and Wyeth-Ayerst Research; is a Member of the Advisory Board for Abbott Laboratories

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  • Cited by (0)

    Address requests for reprints to: Loren Laine, M.D., Gastrointestinal Division, Department of Medicine, University of Southern California School of Medicine, 2025 Zonal Avenue, Los Angeles, California 90033. e-mail: [email protected]; fax: (323) 226-7573.

    ☆☆

    Supported by Merck and Co., Whitehouse Station, New Jersey.

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