Cardiovascular effects of cyclooxygenase-2 inhibitors

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.

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.

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.