Researchers have finally addressed questions about the cardiovascular safety of the nonsteroidal antiinflammatory drug (NSAID) celecoxib (Celebrex), a selective cyclooxygenase 2 (COX-2) inhibitor. Concerns about the risk of cardiovascular thrombotic events were raised in the early 2000s, and the highly potent COX-2 inhibitor rofecoxib (Vioxx) was withdrawn from the market in 2004 because of clinical trial findings indicating that the drug doubled the risk of a myocardial infarction from a clot. Concerns were subsequently raised that the increased risk of thrombotic events might be a class effect and extend to nonselective NSAIDs, too, including over-the-counter products. The Food and Drug Administration, in fact, concluded in 2005 that such a class risk was present, and boxed warnings regarding the possible cardiovascular risk were added to the labeling of celecoxib and other NSAIDs.

In 2006 a large multicenter, randomized, double-blind, noninferiority clinical outcome trial was begun to address these safety concerns. The trial, known as the Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen trial, was published in the December 29, 2016, issue of the New England Journal of Medicine (NEJM). The study involved more than 24,000 patients who were at increased cardiovascular risk and had rheumatoid arthritis or osteoarthritis. Patients were randomly assigned to receive either celecoxib (100 mg twice a day), ibuprofen (600 mg three times a day), naproxen (375 mg twice a day), or placebo. The study found celecoxib to be no worse than either ibuprofen or naproxen in terms of cardiovascular risk. It is thought that the cardiovascular effects from NSAIDs are dose related, but there are insufficient data to determine the exact effect of higher doses of celecoxib in comparison with other NSAIDs; in the NEJM study, not enough patients were advanced to larger dosages (200 mg or 400 mg twice daily) for a safety assessment to be performed.

Prescribers should weigh the benefits and risks of cardiovascular events in each patient before prescribing any NSAID. They should continue to provide information concerning the risk of cardiovascular events as part of patient education.

The revised information on celecoxib can be found in the full prescribing information: http://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020998s050lbl.pdf.