摘要
BACKGROUND: Selective cyclooxygenase-2 (COX-2) in hibitors have come under s crutiny because of reports su- ggesting an increased cardiovascular risk associated with their use. Experimen tal research suggesting that these drugs may contribute to a prothrombotic state providessupport 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 com paring two doses of celecoxib (200 mg or 400 mg twice daily) with placebo for th e prevention of colorectal adenomas. All deaths were categorized as cardiovascul ar 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 com posite cardiovascular end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure was reached in 7 of 679 patients in the pla cebo group (1.0 percent), as compared with 16 of 685 patients receiving 200 mg o f celecoxib twice daily (2.3 percent; hazard ratio, 2.3; 95 percent confidence i nterval, 0.9 to 5.5) and with 23 of 671 patients receiving 400 mg of celecoxib t wice daily (3.4 percent; hazard ratio, 3.4; 95 percent confidence interval,1.4 t o 7.8). Similar trends were observed for other composite end points. On the basi s of these observations,the data and safety monitoring board recommended early d iscontinuation of the study drug. CONCLUSIONS: Celecoxib use was associated with a dose-related increase in the composite end point of death from cardiovascula r causes, myocardial infarction, stroke, or heart failure. In light of recent re ports of cardiovascular harm associated with treatment with other agents in this class, these data provide further evidence that the use of COX-2 inhibitors ma y increase the risk of serious cardiovascular events.
BACKGROUND: Selective cyclooxygenase-2 (COX-2) in hibitors have come under s crutiny because of reports su- ggesting an increased cardiovascular risk associated with their use. Experimen tal research suggesting that these drugs may contribute to a prothrombotic state providessupport 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 com paring two doses of celecoxib (200 mg or 400 mg twice daily) with placebo for th e prevention of colorectal adenomas. All deaths were categorized as cardiovascul ar 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 com posite cardiovascular end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure was reached in 7 of 679 patients in the pla cebo group (1.0 percent), as compared with 16 of 685 patients receiving 200 mg o f celecoxib twice daily (2.3 percent; hazard ratio, 2.3; 95 percent confidence i nterval, 0.9 to 5.5) and with 23 of 671 patients receiving 400 mg of celecoxib t wice daily (3.4 percent; hazard ratio, 3.4; 95 percent confidence interval,1.4 t o 7.8). Similar trends were observed for other composite end points. On the basi s of these observations,the data and safety monitoring board recommended early d iscontinuation of the study drug. CONCLUSIONS: Celecoxib use was associated with a dose-related increase in the composite end point of death from cardiovascula r causes, myocardial infarction, stroke, or heart failure. In light of recent re ports of cardiovascular harm associated with treatment with other agents in this class, these data provide further evidence that the use of COX-2 inhibitors ma y increase the risk of serious cardiovascular events.
