Rofecoxib did not provide unequivocal benefit over traditional NSAIDs

EDITOR—In their editorial Jüni et al say that celecoxib is no safer than diclofenac or ibuprofen and that the CLASS authors “spun” their analysis to suggest otherwise.1 They also state: “In contrast with the CLASS trial, the VIGOR trial, which was similar in design and outcomes, found an unequivocal benefit of another selective COX 2 inhibitor, rofecoxib, over traditional non-steroidal anti-inflammatory agents [NSAIDs].”2

I disagree. Although serious gastrointestinal adverse effects were less frequent in rofecoxib users than in patients with rheumatoid arthritis treated with naproxen (number needed to treat to prevent one serious upper gastrointestinal event 191; 95% confidence interval 114 to 586), rofecoxib was in fact less safe than naproxen. The published version of the VIGOR trial focused on the narrow outcome of serious gastrointestinal complications.

The US Food and Drug Administration took the unprecedented step of presenting its review of both the CLASS trial and the VIGOR trial on its website.3 Review of the complete data presented there shows that when all serious adverse events are included—not just gastrointestinal events—patients treated with naproxen had fewer serious events. Among patients treated with rofecoxib, 9.3% experienced a serious adverse event compared with 7.8% of those treated with naproxen (relative risk 0.81; 0.62 to 0.97). When all serious adverse events are counted, the number needed to harm when rofecoxib is used compared with naproxen is 66 (36 to 332).

The increased risk of serious adverse events was due to an increase of serious adverse cardiovascular events, including a 300% greater risk of myocardial infarction in those treated with rofecoxib.

The VIGOR results, examined fully, show that at least one traditional non-steroidal anti-inflammatory drug—naproxen—is unequivocally safer than rofecoxib, albeit with an increased risk of adverse events limited to the gastrointestinal tract.