Findings from COX 2 studies are released
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《英国医生杂志》
Results from recent studies that raised concerns about the cardiovascular safety of cyclo-oxygenase-2 (COX 2) inhibitors have been made available early, in advance of hearings on the drug class by the US Food and Drug Administration.
All the studies have been published online in the New England Journal of Medicine (http://nejm.org), and the journal lifted its normal embargo date for the studies because of what it described as the "possible public health implications."
The results come immediately before a three-day hearing looking into the benefits and risks of COX 2 inhibitors that is being held by the US Food and Drug Administration's advisory committee, starting on 16 February. Among other things, the advisory committee is expected to evaluate recent data that suggest that, in addition to rofecoxib (Vioxx), other COX 2 inhibitors may be associated with an increased risk of cardiovascular events and to consider changes to the labelling of these medicines.
In one study, Solomon and colleagues 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.
A cardiovascular event occurred in 7 of 679 (1.0%) patients in the placebo group, compared with 16 of 685 (2.3%) patients receiving 200 mg of celecoxib twice daily (hazard ratio 2.3; 95% confidence interval 0.9 to 5.5) and with 23 of 671 (3.4%) patients receiving 400 mg of celecoxib twice daily (3.4; 1.4 to 7.8).
On the basis of these observations, the data and safety monitoring board recommended early discontinuation of the study drug.
In a second study, Bresalier and colleagues report the finding of an increased cardiovascular risk with rofecoxib that prompted the removal of that particular drug from the market by its manufacturer last September ( BMJ 2004;329: 816).
That trial—the APPROVe (adenomatous polyp prevention on Vioxx) trial—is being published for the first time, although the drug manufacturers, Merck, took action on the findings last year. A total of 2586 patients with a history of colorectal adenomas were randomised: 1287 were assigned to receive 25 mg of rofecoxib daily, and 1299 to receive placebo.
A total of 46 patients in the rofecoxib group had a confirmed thrombotic event during 3059 patient years of follow up (1.50 events per 100 patient years), compared with 26 patients in the placebo group during 3327 patient years of follow up (0.78 events per 100 patient years); the corresponding relative risk was 1.92 (95% confidence interval 1.19 to 3.11; P=0.008).
A third study, by Nussmeier and colleagues, shows that short term use of valdecoxib and parecoxib in patients who had had coronary artery bypass grafting was associated with increased cardiovascular risk.(Scott Gottlieb)
All the studies have been published online in the New England Journal of Medicine (http://nejm.org), and the journal lifted its normal embargo date for the studies because of what it described as the "possible public health implications."
The results come immediately before a three-day hearing looking into the benefits and risks of COX 2 inhibitors that is being held by the US Food and Drug Administration's advisory committee, starting on 16 February. Among other things, the advisory committee is expected to evaluate recent data that suggest that, in addition to rofecoxib (Vioxx), other COX 2 inhibitors may be associated with an increased risk of cardiovascular events and to consider changes to the labelling of these medicines.
In one study, Solomon and colleagues 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.
A cardiovascular event occurred in 7 of 679 (1.0%) patients in the placebo group, compared with 16 of 685 (2.3%) patients receiving 200 mg of celecoxib twice daily (hazard ratio 2.3; 95% confidence interval 0.9 to 5.5) and with 23 of 671 (3.4%) patients receiving 400 mg of celecoxib twice daily (3.4; 1.4 to 7.8).
On the basis of these observations, the data and safety monitoring board recommended early discontinuation of the study drug.
In a second study, Bresalier and colleagues report the finding of an increased cardiovascular risk with rofecoxib that prompted the removal of that particular drug from the market by its manufacturer last September ( BMJ 2004;329: 816).
That trial—the APPROVe (adenomatous polyp prevention on Vioxx) trial—is being published for the first time, although the drug manufacturers, Merck, took action on the findings last year. A total of 2586 patients with a history of colorectal adenomas were randomised: 1287 were assigned to receive 25 mg of rofecoxib daily, and 1299 to receive placebo.
A total of 46 patients in the rofecoxib group had a confirmed thrombotic event during 3059 patient years of follow up (1.50 events per 100 patient years), compared with 26 patients in the placebo group during 3327 patient years of follow up (0.78 events per 100 patient years); the corresponding relative risk was 1.92 (95% confidence interval 1.19 to 3.11; P=0.008).
A third study, by Nussmeier and colleagues, shows that short term use of valdecoxib and parecoxib in patients who had had coronary artery bypass grafting was associated with increased cardiovascular risk.(Scott Gottlieb)