Gastrointestinal safety of coxibs and outcomes studies: what's the verdict?

Abstract

Although nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used, their main limitation is gastrointestinal (GI) injury. Two double-blind, randomized, outcomes trials were conducted to determine the incidence of clinical GI events with the coxibs, rofecoxib and celecoxib, compared with nonselective NSAIDs. The VIGOR study (VIOXX Gastrointestinal Outcomes Research) compared rofecoxib with naproxen, and the CLASS study (Celecoxib Long-term Arthritis Safety Study) compared celecoxib with ibuprofen and diclofenac. The VIGOR trial revealed a relative risk reduction for clinical upper GI events of 50% with rofecoxib, and a 60% reduction in complicated events. In the CLASS study, the 23% reduction in complicated ulcers with celecoxib did not reach statistical significance (P = 0.45), although when all clinical events were examined, the 34% reduction was significant (P = 0.04). However, low-dose aspirin use, which was allowed in the CLASS study, may have influenced the results. A subgroup analysis in the patients who did not take aspirin revealed a nonsignificant 45% reduction in complicated events with celecoxib (P = 0.19), and a 47% reduction in complicated and symptomatic ulcers (P = 0.02).