Risk of adverse cardiovascular reactions with Cox-2 Inhibitors

COX-2 selective inhibitor is a form of NSAID (Non-steroidal anti-inflammatory) drugs targeting the COX-2 enzyme which is responsible for inflammation and pain.

Rofecoxib is a Cox-2 Inhibitor developed by Merck & Co. to treat osteoarthritis, acute pain conditions, and dysmenorrhoea. Rofecoxib was approved as safe and effective by the FDA on May 20, 1999 and was subsequently marketed under the brand name Vioxx, Ceoxx and Ceeoxx.

On September 30, 2004, Merck voluntarily withdrew rofecoxib from the market because of concerns about increased risk of heart attack and stroke associated with Vioxx. Rofecoxib was one of the most widely used drugs ever to be withdrawn from the market. In the year before withdrawal, Merck had sales revenue of $2.5 billion from Vioxx.

According to the Journal of American Medical Association (JAMA), Rofecoxib increases the risk of acute MI at low and high doses. This risk begins early in therapy, probably with the first dose. There is no initial 18-month period of immunity from risk. Celecoxib also increases risk at doses higher than 200 mg/d; at lower doses, the potential risk is less clear. Several other NSAIDs increase risk, including the COX-2 selective NSAIDs diclofenac and meloxicam, and the nonselective NSAID indomethacin, and probably ibuprofen. Meta-analyses of randomized clinical trials and observational studies agree that naproxen is neutral for MI risk.

On January 24, 2005, Public Citizen petitioned the FDA to immediately remove Celebrex and Bextra, two other Cox-2 inhibitors from the market because they increase the risk of heart attacks in patients. The group also urged the FDA to cancel plans to approve two other drugs in the same class. Public Citizen’s petition on Celebrex and Bextra examines the results of 14 randomized control trials involving the five COX-2 inhibitors, as well as other published and unpublished scientific information. The other two COX-2 inhibitors are Prexige (lumiracoxib) and Arcoxia (etoricoxib), neither of which has been approved for sale by the FDA. The petition says that clinical studies suggest these drugs exhibit the same cardiovascular toxicity as Vioxx, Celebrex and Bextra, and should not be approved.

Below is our ADRS chart for the 2nd quarter of 2007 with Celebrex against the background of all drugs. The chart is quite revealing. We have noted the reactions associated with cardiovascular risks Celebrex, another Cox-2 inhibitor drug.