Background: Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) inhibit both cyclo-oxygenase (COX) isoenzymes, i.e. COX-1 and COX-2. Rofecoxib, an agent that selectively inhibits COX-2, has been shown to provide equivalent anti-inflammatory and analgesic efficacy to comparator non-selective NSAIDs in osteoarthritis (OA) and other pain models with a significant improvement in gastrointestinal (GI) safety and tolerability. Based on renal physiology studies, it was predicted that rofecoxib would have renovascular effects similar to those observed with non-selective NSAIDs -specifically edema, blood pressure elevation, attenuation of the effects of ACE inhibitors, and (in rare circumstances), acute renal failure might be manifest in a small percentage of patients.

Objective: To assess the renovascular safety profile of rofecoxib in OA patients compared to that of non-selective NSAID comparators.

Methods: Renovascular adverse experiences (AEs) in over 5000 participants in Phase IIb/III OA clinical trials were reviewed and compared between rofecoxib and non-selective NSAID comparators (ibuprofen 800mg tid, diclofenac 50mg tid, nabumetone 1500mg qd).

Results: The incidence of lower extremity edema (LEE) AEs was generally similar between rofecoxib 12.5mg/day, rofecoxib 25mg/day, and non-selective comparator NSAIDs. Treatment discontinuations due to LEE AEs and clinically significant weight gain (> 2 kg) associated with LEE AEs were infrequent and generally similar in all active treatment groups. Congestive heart failure (CHF) was rare in all treatment groups. The incidence of hypertension AEs was low in all active treatment groups. Discontinuations due to hypertension AEs and hypertension AEs requiring a change or adjustment in blood pressure medications were similar and uncommon in all treatment groups. There was only a single report of acute renal failure (in the ibuprofen treatment group).

Conclusions: In the rofecoxib phase IIb/III OA database, the renal safety profile for rofecoxib, a selective inhibitor of COX-2, was generally similar to that of the comparator, non-selective NSAIDs which were studied.