NSAIDs and COX-2 inhibitors: what can we learn from large outcomes trials?The gastroenterologist's perspective

Many studies have shown that a variety of strategies, including the use of cyclooxygenase-2 (COX-2) inhibitors, or co-prescription of misoprostol or p roton pump inhibitors, result in reduced endoscopic damage and ulceration c ompared with non-selective nonsteroidal anti-inflammatory drugs (NSAIDs) al one. Questions have been raised as to whether this would translate into imp roved clinical outcomes. Consequently, several studies have investigated whether use of COX-2 inhibi tors (Vioxx(R) Gastrointestinal Outcomes Research [VIGOR] and the Celecoxib Long-Term Arthritis Safety Assessment Study [CLASS] studies) or co-prescri ption with misoprostol (MUCOSA) would reduce the event rate of clinically s ignificant ulcers. These studies have shown an approximate halving of such events. They have raised the possibility that use of low dose aspirin may c ompromise these benefits and appear to have shown differences between (at l east some) COX-2 inhibitors and (at least some) NSAIDs with regard to myoca rdial infarction. Among the lessons learned from this experience are the need to define close ly the outcomes of interest and possibly to concentrate on ulcer complicati ons, the need for adequately powered studies, and the fact that endoscopic studies broadly predict outcomes. However, there are differences in the est imated rates of reduction. It is not self evident whether outcomes studies or endoscopic studies give a truer estimate of risk. A helpful development would be more standardized gastrointestinal assessment at the time of ulcer complications and this could be achieved if studies were done in countries with well-developed primary care systems.