Cardiovascular effects of cyclooxygenase-2 inhibitors.
OBJECTIVE
Arthritis and musculoskeletal disorders are highly prevalent and management often involves the use of nonsteroidal antiinflammatory drugs. Cyclooxygenase-2 enzyme inhibitors are newer selective nonsteroidal antiinflammatory drugs that purport to exhibit less gastrointestinal toxicity than traditional nonsteroidal antiinflammatory drugs. Cardiotoxicity has been an adverse outcome of cyclooxygenase-2 inhibitors and this article will critically review the evidence.


RESULTS
Although there is less than perfect evidence, both traditional nonsteroidal antiinflammatory drugs, with the possible exception of naproxen, and cyclooxygenase-2 inhibitors are associated with increased thrombotic cardiovascular risk. There is strong evidence supporting the cardiotoxicity of rofecoxib and valdecoxib, but less compelling evidence for the other cyclooxygenase-2 inhibitors. Observational studies have been helpful in providing confirmatory and complimentary evidence about this cardiotoxicity. The thrombotic cardiovascular risk begins upon drug introduction, continues throughout exposure and is greatest in patients with a high baseline cardiac risk profile. Cyclooxygenase-2 inhibitors are also associated with other nonthrombotic cardiovascular risks.


CONCLUSIONS
The totality of the evidence suggests that all cyclooxygenase-2 inhibitors are associated with increased cardiotoxicity. The cardiovascular risks of the different cyclooxygenase-2 inhibitors are not homogeneous, however, and are likely influenced not only by a class effect, but also by individual drug, dosage and patient characteristics.
Brophy
James M
JM
Department of Medicine, McGill University Health Centre, McGill University, Montréal, Québec, Canada. james.brophy@mcgill.ca
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007783:Lactones / Q000009:adverse effects / Q000494:pharmacology; D011720:Pyrazoles / Q000009:adverse effects / Q000494:pharmacology; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D013449:Sulfonamides / Q000009:adverse effects / Q000494:pharmacology; D013450:Sulfones / Q000009:adverse effects / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D000068579:Celecoxib