Selective COX-2 Inhibitors and Risk of Cardiovascular Events

onsteroidal anti-inflammatory drugs (NSAIDs) are prescribed commonly for the treatment of pain and inflammation caused by various musculoskeletal disorders and dysmenorrhea. Nonselective NSAIDs’ anti-inflammatory effects appear to be caused by blocking the enzyme cyclooxygenase-2 (COX-2). In addition, nonselective NSAIDs exert both their antiplatelet and detrimental effects on the gastrointestinal mucosa by blocking COX-1. 1 COX-2 inhibitors were developed as a safer alternative to traditional NSAIDs because there was less risk of gastrointestinal ulceration. Recently, concern that COX-2 inhibitors may contribute to the onset of acute myocardial infarction (MI) and thromboembolic events has led to several trials, which have yielded conflicting results regarding the effect that COX-2‐specific inhibitors versus traditional NSAIDs have on cardiovascular events. The Celecoxib Long-term Arthritis Safety Study (CLASS) trial showed no difference in the rate of MI in patients taking a COX-2 inhibitor (celecoxib) and those taking NSAIDs (either ibuprofen or diclofenac). 2 Conversely, the Vioxx Gastrointestinal Outcomes Research (VIGOR) study, which compared rofecoxib (a COX-2 inhibitor) with naproxen (a nonselective NSAID), found that MIs were more frequent in patients treated with rofecoxib than in patients treated with naproxen. 3 Was this difference due to a detrimental effect of rofecoxib or a beneficial effect of naproxen due to platelet inhibition? This review article discusses the implications of the CLASS and VIGOR studies and analyzes other studies that examine the association between NSAIDs and MIs as well as other acute thromboembolic events.