Celecoxib nearly doubled CV risk in halted trials.(Clinical Rounds)

LOS ANGELES -- Celecoxib cannot be recommended to reduce colorectal cancer risk--despite its proven efficacy for that indication--until more is known about its potential cardiovascular risks, coordinators of two chemoprevention trials have concluded.

Composite data from the international Prevention of Spontaneous Adenomatous Polyps (PreSAP) study and the Adenoma Prevention with Celecoxib (APC) trial revealed nearly a twofold risk in cardiovascular events in patients taking celecoxib at doses of 200 mg or 400 mg twice daily or 400 mg once daily, compared with patients assigned to placebo in the trials.

"Celecoxib cannot currently be recommended for the prevention of sporadic adenomas until we understand more clearly its potential cardiovascular toxicity and the mechanisms that underlie this," said Dr. Bernard Levin, vice president of the division of cancer prevention at the University of Texas M.D. Anderson Cancer Center, Houston.

Reporting on the composite results at the annual Digestive Disease Week, Dr. Levin stressed that there was a low absolute number of cardiovascular deaths and nonfatal cardiovascular events in both the celecoxib and placebo groups.

"Both the APC and PreSAP studies were designed with high statistical power to assess the effect on polyp recurrence. However, the analysis of cardiac events--although it was blinded and based on pre-specified outcomes--was based on few events and has limited statistical power," he said.

The 51 events among 2,289 patients taking any dose of celecoxib included cardiovascular death and nonfatal myocardial infarction, stroke, or heart failure.

The hazard ratios for increased cardiovascular events among the trials and dosages were: