title: Cardiovascular issues of COX-2 inhibitors and NSAIDs.
abstract: 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  Rofecoxib (Vioxx) was withdrawn from the market because of increased death from cardiovascular (CV) events.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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Rheumatology, St Vincent's Hospital, Melbourne, Victoria. melinda.wong@svhm.org.au
authors.forename: Melinda
authors.initials: M
authors.lastname: Wong
authors.forename: Phil
authors.initials: P
authors.lastname: Chowienczyk
authors.forename: Bruce
authors.initials: B
authors.lastname: Kirkham
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D002985:Clinical Protocols; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007783:Lactones / Q000009:adverse effects; D051437:Renal Insufficiency / Q000139:chemically induced; D018570:Risk Assessment; D013450:Sulfones / Q000009:adverse effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib