Warnings issued over COX 2 inhibitors in US and UK
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《英国医生杂志》
Warnings were issued last month about two COX 2 (cyclo-oxygenase-2) inhibitors because of fears that they might increase the risk of cardiovascular events, including heart attacks and strokes.
Celecoxib (Celebrex) showed an increased risk of cardiovascular events in a long term study (sponsored by the US National Cancer Institutes) that looked at use of the drug for prevention of colon cancer.
Patients in the five year trial taking 400 mg/day or 800 mg/day of celecoxib had, respectively, a 2.5-fold and 3.4-fold increased risk of a major cardiovascular event compared with placebo. The Food and Drug Administration and the National Cancer Institutes announced jointly that 2.2% of patients given 400 mg/day and 3% of patients given 800 mg/day had a cardiovascular event, compared with 0.9% of patients taking placebo.
The trial involved 2400 patients, who took the drug for an average of 33 months. It has now been suspended.
Pfizer said that results from a long term, company sponsored trial of celecoxib in patients with cancer—known as the PreSAP study—had shown no greater risk of cardiovascular events in patients receiving celecoxib than in those receiving placebo. A third study, which has enrolled about 2000 patients at high risk of Alzheimer's disease, was reviewed by a data monitoring board on 10 December and allowed to continue with no changes.
Pfizer said that for now it would not withdraw celecoxib from the market. The FDA said that "all regulatory options" were still possible. In the mean-time, the FDA's commissioner, Dr Lester Crawford, said that the FDA is advising physicians to consider alternatives to celecoxib and patients to consult their doctors.
Professor Gordon Duff, chairman of the British Committee on the Safety of Medicines, has sent an urgent email to all doctors in the United Kingdom, saying that any patients with established ischaemic heart disease or cerebrovascular disease who are being treated with any COX 2 inhibitor should be switched to alternative (non-COX 2 selective) treatments as soon as is convenient.
A letter to the New England Journal of Medicine released on the journal's website last month said that another COX 2 inhibitor, valdecoxib (Bextra), carries the same risks of increased cardiovascular outcomes of stroke and myocardial infarction as celecoxib and rofecoxib (Vioxx) and should be taken off the market. Rofecoxib was withdrawn from the market by its manufacturer, Merck, in September ( BMJ 2004;329: 816).
"To protect the safety of the public, we write to recommend that clinicians stop prescribing valdecoxib except in extraordinary circumstances.
"This recommendation is based on the long delay between the initial evidence of the cardiotoxicity of rofecoxib and its withdrawal, recent studies demonstrating the cardiotoxicity of valdecoxib in high-risk patients, the availability of other therapies not currently known to have cardiovascular risks, and the lack of compelling evidence of countervailing benefits," the authors wrote ( New England Journal of Medicine 2004;351: 2767).(Scott Gottlieb)
Celecoxib (Celebrex) showed an increased risk of cardiovascular events in a long term study (sponsored by the US National Cancer Institutes) that looked at use of the drug for prevention of colon cancer.
Patients in the five year trial taking 400 mg/day or 800 mg/day of celecoxib had, respectively, a 2.5-fold and 3.4-fold increased risk of a major cardiovascular event compared with placebo. The Food and Drug Administration and the National Cancer Institutes announced jointly that 2.2% of patients given 400 mg/day and 3% of patients given 800 mg/day had a cardiovascular event, compared with 0.9% of patients taking placebo.
The trial involved 2400 patients, who took the drug for an average of 33 months. It has now been suspended.
Pfizer said that results from a long term, company sponsored trial of celecoxib in patients with cancer—known as the PreSAP study—had shown no greater risk of cardiovascular events in patients receiving celecoxib than in those receiving placebo. A third study, which has enrolled about 2000 patients at high risk of Alzheimer's disease, was reviewed by a data monitoring board on 10 December and allowed to continue with no changes.
Pfizer said that for now it would not withdraw celecoxib from the market. The FDA said that "all regulatory options" were still possible. In the mean-time, the FDA's commissioner, Dr Lester Crawford, said that the FDA is advising physicians to consider alternatives to celecoxib and patients to consult their doctors.
Professor Gordon Duff, chairman of the British Committee on the Safety of Medicines, has sent an urgent email to all doctors in the United Kingdom, saying that any patients with established ischaemic heart disease or cerebrovascular disease who are being treated with any COX 2 inhibitor should be switched to alternative (non-COX 2 selective) treatments as soon as is convenient.
A letter to the New England Journal of Medicine released on the journal's website last month said that another COX 2 inhibitor, valdecoxib (Bextra), carries the same risks of increased cardiovascular outcomes of stroke and myocardial infarction as celecoxib and rofecoxib (Vioxx) and should be taken off the market. Rofecoxib was withdrawn from the market by its manufacturer, Merck, in September ( BMJ 2004;329: 816).
"To protect the safety of the public, we write to recommend that clinicians stop prescribing valdecoxib except in extraordinary circumstances.
"This recommendation is based on the long delay between the initial evidence of the cardiotoxicity of rofecoxib and its withdrawal, recent studies demonstrating the cardiotoxicity of valdecoxib in high-risk patients, the availability of other therapies not currently known to have cardiovascular risks, and the lack of compelling evidence of countervailing benefits," the authors wrote ( New England Journal of Medicine 2004;351: 2767).(Scott Gottlieb)