What have we learned from the large outcomes trials of COX-2 selective inhibitors? The rheumatologist's perspective

The cyclooxygenase (COX)-2 selective inhibitors celecoxib and, rofecoxib ha ve been found to be more, effective than placebo-and comparable effective t o nonselective nonsteroidal antiinflammatory drugs: (NSAIDs) in the treatme nt of patients with osteoarthritis and rheumatoid arthritis. Two large outc ome studies, the Celecoxib Longterm Arthritis Safety Study (CLASS) and Viox x Gastrointestinal Outcomes Research (WIGOR) trial, were conducted to test the hypothesis that patients receiving a COX-2 selective inhibitor would ha ve significantly fewer clinically important upper gastrointestinal events t han patients taking nonselective NSAIDs. This article critically reviews th e design and results of these trials. Both trials found that arthritis patients not taking low-dose aspirin (325 mg/ day or less) who were randomized to receive COX-2 selective inhibitors had significantly fewer symptomatic and complicated ulcers than patients ra ndomized to nonselective NSAIDs. A, significant risk reduction was not demo nstrated, however; in patients in the CLASS trial who were taking low-dose aspirin, itself an independent risk factor for the endpoint. These data val idate the COX-2 hypothesis and support recommendations that a COX-2 selecti ve inhibitor should be used in the treatment of patients at increased risk for symptomatic and complicated ulcers. Further studies are needed to determine whether COX-2 selective inhibitors are safer than nonselective NSAIDs when used in patients receiving low-dose aspirin. The COX-2 selective inhibitors have a similar profile of renal ad verse events to nonselective NSAIDs. The increased rate of cardiovascular t hromboembolic adverse events among patients randomized to rofecoxib compare d to those randomized to naproxen in the VIGOR trial is consistent with the lack of an antiplatelet effect for this COX-2 selective inhibitor This emp hasizes the need for the use of low dose aspirin in patients at risk for su ch, events, especially myocardial infarction.