title: An evidence-based evaluation of the gastrointestinal safety of coxibs.
abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) are nonselective inhibitors of cyclooxygenase (COX) isoforms COX-1 and COX-2. NSAIDs have analgesic and anti-inflammatory properties that are proven, and they are extensively used in the treatment of arthritis, pain, and headache. Despite their good efficacy, NSAIDs are associated with significant gastrointestinal (GI) toxicity, which appears to be related to the inhibition of the cytoprotective function of COX-1. Thus, selective COX-2 inhibitors, or coxibs, were designed to inhibit only the production of COX-2-dependent inflammatory prostaglandins, without any effect on COX-1 and its gastroprotective function. This article reviews important evidence on the GI safety of coxibs. Endoscopic studies demonstrated that coxibs, such as celecoxib and rofecoxib, induced significantly fewer ulcers than nonspecific NSAIDs. To analyze whether the incidence of clinical GI events is also lower with coxibs, 2 large controlled clinical trials, the Celecoxib Long-term Arthritis Safety Study (CLASS) and Vioxx Gastrointestinal Outcomes Research (VIGOR), evaluated the GI safety of celecoxib and rofecoxib, respectively. Based on evidence from the VIGOR trial, it was demonstrated that rofecoxib has already fulfilled the promise and significantly decreases the risk of clinically important and complicated GI events compared with a nonselective NSAID, naproxen. In contrast, the CLASS trial showed that the incidence of ulcer complications in patients treated with celecoxib was similar in patients treated with nonspecific NSAIDs.
authors.affiliation: Division of Clinical Decision Making and Health Care, Toronto General Research Institute, Toronto General Hospital, Toronto, Ontario, Canada. claire.bombardier@utoronto.ca
authors.forename: Claire
authors.initials: C
authors.lastname: Bombardier
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001168:Arthritis / Q000188:drug therapy; D002319:Cardiovascular System / Q000187:drug effects / Q000201:enzymology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D004341:Drug Evaluation / Q000379:methods; D019317:Evidence-Based Medicine / Q000379:methods*; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D012307:Risk Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases