Celecoxib prevents colorectal adenoma, but raises CVD risk
Last Updated: 2006-08-30 18:57:52 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Two international clinical trials that included thousands of patients have documented the ability of celecoxib to reduce the recurrence of colorectal adenomas for at least 3 years after polypectomy. However, the trials also confirmed the dose-dependent increased risk of severe cardiovascular events associated with celecoxib.
Both trials, reported in The New England Journal of Medicine for August 31, included patients who had undergone polypectomy within months of enrollment. Repeat colonoscopies were performed at year 1 and year 3. The risk of severe cardiovascular events linked to celecoxib led to early suspension of both studies.
In the Adenoma Prevention with Celecoxib trial, led by Dr. Monica M. Bertagnolli at Brigham and Women's Hospital in Boston, 2035 patients were randomly assigned to 200 mg celecoxib bid; 400 mg celecoxib bid, or placebo.
The cumulative incidence of new adenomas was 60.7% in the placebo group, 43.2% in the low-dose celecoxib group, and 37.5% in the high-dose group. Corresponding rates of advanced adenomas were 17.2%, 7.8% and 6.3%. Active treatment was also associated with a lower adenoma burden, defined as the sum of the diameter of all adenomas.
However, the rates of serious cardiovascular events, including nonfatal MI, stroke, heart failure, or death, were 2.0%, 2.6% and 3.4%, respectively. The risk of these events was greatest among patients with a history of cardiovascular events at baseline.
Similar results were obtained by Dr. Bernard Levin, from the University of Texas M. D. Anderson Cancer Center in Houston, and other members of the Prevention of Colorectal Sporadic Adenomatous Polyps. The efficacy analysis involved 840 subjects randomly assigned to celecoxib 400 mg qd, and 557 to placebo.
Cumulative rates of adenoma at 3 years were 33.6% in the celecoxib group and 49.3% in the placebo group. The risk of advanced adenoma was approximately doubled in the placebo group, as was the overall burden of disease.
Serious cardiovascular events occurred in 1.9% of those in the placebo group and 2.5% of those in the celecoxib group.
Editorialists, Dr. Bruce M. Psaty and Dr. John D. Potter praise both trials for reporting the efficacy and safety profiles for patients at risk of recurrent adenomas for the first time.
However, the physicians, from the University of Washington in Seattle, add that "the increased incidence of cardiovascular events caused by celecoxib outweighs what may be an optimistic projection of its potential benefit in decreasing colorectal-cancer events."
They therefore agree with the trial authors that the drug "has no role as a chemopreventive agent either in patients with nonfamilial colonic adenomas or in the general population."
