Celecoxib associated with lower rate of renal dysfunction compared to nonspecific inhibitor NSAIDs

Abstract

Both the COX-1 and COX-2 isoforms are expressed by the human kidney and vasculature. Therefore, it is important to evaluate the renovascular effects of COX-2 specific inhibitors and NSAIDs, particularly in patients with preexisting renal dysfunction. The Celecoxib Long-term Arthritis Safety Study (CLASS) assessed gastrointestinal outcomes associated with supratherapeutic doses of the COX-2 specific inhibitor celecoxib (400mg bid), and standard doses of NSAIDs, ibuprofen (800mg tid) and diclofenac (75mg bid), in patients with rheumatoid arthritis (RA) or osteoarthritis (OA). The trial's full database provided a large cardiorenal database for studying renal-related adverse events associated with nonspecific NSAIDs and celecoxib. Complete methods and gastrointestinal and cardiovascular results are published elsewhere. Enrolled patients had a serum creatinine ≤1.5mg/dL reflecting normal renal function. Renal function was assessed in all patients including those with mild prerenal azotemia defined by a baseline blood urea nitrogen (BUN) level of >20mg/dL. The renovascular effects measured in these patients were clinically important reductions in renal function (defined as an increase in serum creatinine >0.5mg/dL from baseline) and mean serum creatinine/estimated creatinine clearance. In patients with mild prerenal azotemia significantly fewer patients taking celecoxib exhibited clinically important reductions in renal function (3.4%) compared with either diclofenac (8.3%;P ≤0.05) or ibuprofen (7.7%;P ≤0.05). In patients with mild renal compromise, celecoxib was associated with a significantly lower rate of renal dysfunction at supratherapeutic doses compared with diclofenac and ibuprofen at standard doses. These data suggest that celecoxib may be a more suitable alternative to treat chronic pain and inflammation than nonspecific NSAIDs in patients with compromised renovascular function. (See Table) *P ≤ 0.05; ANCOVA, Fisher's exact test *P ≤ 0.05; ANCOVA, Fisher's exact test