Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention.
BACKGROUND
Selective cyclooxygenase-2 (COX-2) inhibitors have come under scrutiny because of reports suggesting an increased cardiovascular risk associated with their use. Experimental research suggesting that these drugs may contribute to a prothrombotic state provides support for this concern.


METHODS
We reviewed all potentially serious cardiovascular events among 2035 patients with a history of colorectal neoplasia who were enrolled in a trial comparing two doses of celecoxib (200 mg or 400 mg twice daily) with placebo for the prevention of colorectal adenomas. All deaths were categorized as cardiovascular or noncardiovascular, and nonfatal cardiovascular events were categorized in a blinded fashion according to a prespecified scheme.


RESULTS
For all patients except those who died, 2.8 to 3.1 years of follow-up data were available. A composite cardiovascular end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure was reached in 7 of 679 patients in the placebo group (1.0 percent), as compared with 16 of 685 patients receiving 200 mg of celecoxib twice daily (2.3 percent; hazard ratio, 2.3; 95 percent confidence interval, 0.9 to 5.5) and with 23 of 671 patients receiving 400 mg of celecoxib twice daily (3.4 percent; hazard ratio, 3.4; 95 percent confidence interval, 1.4 to 7.8). Similar trends were observed for other composite end points. On the basis of these observations, the data and safety monitoring board recommended early discontinuation of the study drug.


CONCLUSIONS
Celecoxib use was associated with a dose-related increase in the composite end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure. In light of recent reports of cardiovascular harm associated with treatment with other agents in this class, these data provide further evidence that the use of COX-2 inhibitors may increase the risk of serious cardiovascular events.
Solomon
Scott D
SD
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ssolomon@rics.bwh.harvard.edu
McMurray
John J V
JJ
Pfeffer
Marc A
MA
Wittes
Janet
J
Fowler
Robert
R
Finn
Peter
P
Anderson
William F
WF
Zauber
Ann
A
Hawk
Ernest
E
Bertagnolli
Monica
M
D018256:Adenomatous Polyps / Q000517:prevention & control*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000401:mortality; D000068579:Celecoxib; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012306:Risk; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib