Lessons learned from troubles with COX-2 inhibitors

One of the nation’s leading cardiovascular medical researchers has issued a call for less aggressive direct-to-consumer advertising and better safety assurances of medications in a special article posted online by JAMA because of its relevance to the recent withdrawals and warning labels on the pain-relieving drugs known as COX-2 inhibitors. The article will be published in a print edition of JAMA in early 2005.

Eric J. Topol, M.D., from the Cleveland Clinic Foundation, writes that the cardiovascular risks of the various coxib drugs were not well-studied in clinical trials. “Based on data available in 2001 for celecoxib and rofecoxib, my colleagues and I concluded: ‘it is mandatory to conduct a trial specifically assessing cardiovascular risk and benefit of these agents. Until then, we urge caution in prescribing these agents to patients at risk for cardiovascular morbidity.’ Unfortunately, no such trials were ever initiated and the official warnings for the coxib drugs took years to materialize.”

“Importantly, providing more authority to the FDA (Food and Drug Administration) to shape and require the execution of vital trials is perhaps the most important lesson from the coxibs,” Dr. Topol writes.

“… legislation is needed to empower the FDA to require industry to conduct trials that are deemed necessary to ensure the safety profile of a drug. Had coxib trials been conducted five years ago in patients with established cardiovascular disease, when the benefit and risks were indeterminate, clinicians would have quickly learned the risk and potentially avoided a major cardiovascular calamity. The combination of mass promotion of a medicine with an unknown and suspect safety profile cannot be tolerated in the future. An aggressive position going forward is necessary for not only ensuring the safety of prescription medicines, but also to restore a solid foundation of public trust.”