Although specifically designed to avoid the gastrointestinal side effects associated with non-selective NSAIDs, our analysis shows that cyclooxygenase-2 (COX-2) inhibitors are associated with an increased risk of upper gastrointestinal adverse events (AEs), especially abdominal pain, when used to treat pain in osteoarthritis (OA).

As expected, COX-2 inhibitors were associated with an increased risk of cardiovascular AEs; the risk of heart failure and edema remained significant even when rofecoxib was removed from the analysis.

These results confirm that a cautious approach to the use of COX-2 inhibitors (as for other NSAIDs) for the symptomatic management of pain and inflammation in OA is advisable, limiting use to intermittent or cyclical use rather than chronic treatment in order to minimize safety concerns.