Background: Rofecoxib (Vioxx) was withdrawn from the market because of increased death from cardiovascular (CV) events. Other selective cyclooxygenase-2 (COX-2) inhibitors and traditional nonsteroidal anti-inflammatory drugs (NSAIDs) may share this risk, but to what extent is unclear.
Objective: This article reviews the available evidence using a PubMed search for increased CV risk with COX-2 inhibitors and NSAIDs, explores possible mechanisms, and makes recommendations for their appropriate use in clinical practice.
Discussion: Rofecoxib, celecoxib, and the combination of valdecoxib and parecoxib have been found in prospective trials to increase CV risk. NSAIDs have also been found to be associated with increased CV risk in observational studies, but large randomised controlled trials with adequate follow up are required to further investigate this. Recommendations are to use drugs at lowest dose and for shortest duration possible. In patients with or at high risk for CV disease, COX-2 inhibitors are contraindicated. A traditional NSAID plus proton pump inhibitor may be used, but with caution.