The safety of lumiracoxib when used in the treatment of arthritis

The gastrointestinal (GI) adverse effects of NSAIDs are generally considered to be partly due to the inhibition of COX-1 in the GI tract. Therefore, it was anticipated that there would be fewer such events with the selective COX-2 inhibitors. However, selective COX-2 inhibitors will probably lack the cardio-protective effects associated with COX-1 inhibition. The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) evaluated the ulcer complications and cardiovascular outcomes with the use of the selective COX-2 inhibitor, lumiracoxib, versus naproxen/ibuprofen in the treatment of osteoarthritis. Patients (similar to 18,000) received either lumiracoxib 400 mg/day, naproxen 500 mg b.i.d. or ibuprofen 800 mg t.i.d. for 52 weeks. The primary end point was difference in time-to-event distribution of definite or probable upper GI ulcer complications, and these were lower in the lumiracoxib (29 of 9117) than in the ibuprofen (33 of 4397) or naproxen (50 of 4730) groups. The benefit with lumiracoxib was mainly due to a reduced risk of faeces containing blood and of the laboratory evidence of bleeding, and occurred in the population not taking aspirin, but not in the patients taking aspirin. The primary cardiovascular end point was the composite of non-fatal and silent myocardial infarction, stroke or cardiovascular death, and this did not differ between lumiracoxib and naproxen/ibuprofen. However, there were slightly more end points with lumiracoxib (85) than with naproxen/ibuprofen (75), and this nonsignificant difference was due to fewer end points in the naproxen group. Although TARGET establishes the GI safety of lumiracoxib, questions about the cardiovascular outcomes with COX-2 inhibitors, including lumiracoxib, especially in the absence of low-dose aspirin, remain.