Cox-2抑制剂与心血管事件发生率增加有关(上)
A more accurate analysis would compare the patients in CLASS not taking aspirin to the placebo group from the aspirin trials, Dr. Geis said. Using that method, the rate of heart attacks among Celebrex users would be 0.33%. "That's 60% lower than the incidence rate reported for all patients by the authors," he said.
Merck & Co., maker of Vioxx, released a statement saying that based on both the published analysis and Merck's own large-scale-placebo controlled trials, "Merck does not believe the authors' conclusions in the article are scientifically supported by the totality of the data available."
Dr. Laura Demopoulos, senior director of cardiovascular clinical research at Merck, said that the authors made some fundamental mistakes and also overlooked several studies that demonstrated no increased cardiovascular risk for Vioxx. She said that Merck "was aware that the Cleveland Clinic was looking at some data" and that she was aware of meetings between the Clinic investigators and some company representatives, so she was doubly surprised "that they excluded studies that were favorable to Vioxx."
Dr. Demopoulos said Merck has cardiovascular data from 19 controlled clinical studies of rofecoxib that involved more than 28,000 patients. She said the results of those studies demonstrated that the relative risk of cardiovascular events was similar for Vioxx versus placebo as well as for ibuprofen, diclofenac and nabumetone. She said those data were presented to a US Food and Drug Administration advisory panel in February and that Dr. Nissen was a member of that panel.
In their JAMA report, Dr. Nissen and his colleagues also present data from two unpublished trials of rofecoxib, submitted to the US Food and Drug Administration, that allowed the use of low-dose aspirin.
These studies "did not demonstrate the significant increase in cardiovascular event rate noted in VIGOR," they say. However, they note that the trials "had smaller sample sizes [approximately 1000 patients each], used only 25% of the dose of rofecoxib used in VIGOR, and had few events for meaningful comparison. Thus the prothrombotic effect seen with rofecoxib may potentially be dose dependent."
The authors also searched the FDA Adverse Event Reporting System in 2001 and found that 99 thrombotic or embolic events had been attributed to rofecoxib and 102 to celecoxib in the US., 百拇医药
Merck & Co., maker of Vioxx, released a statement saying that based on both the published analysis and Merck's own large-scale-placebo controlled trials, "Merck does not believe the authors' conclusions in the article are scientifically supported by the totality of the data available."
Dr. Laura Demopoulos, senior director of cardiovascular clinical research at Merck, said that the authors made some fundamental mistakes and also overlooked several studies that demonstrated no increased cardiovascular risk for Vioxx. She said that Merck "was aware that the Cleveland Clinic was looking at some data" and that she was aware of meetings between the Clinic investigators and some company representatives, so she was doubly surprised "that they excluded studies that were favorable to Vioxx."
Dr. Demopoulos said Merck has cardiovascular data from 19 controlled clinical studies of rofecoxib that involved more than 28,000 patients. She said the results of those studies demonstrated that the relative risk of cardiovascular events was similar for Vioxx versus placebo as well as for ibuprofen, diclofenac and nabumetone. She said those data were presented to a US Food and Drug Administration advisory panel in February and that Dr. Nissen was a member of that panel.
In their JAMA report, Dr. Nissen and his colleagues also present data from two unpublished trials of rofecoxib, submitted to the US Food and Drug Administration, that allowed the use of low-dose aspirin.
These studies "did not demonstrate the significant increase in cardiovascular event rate noted in VIGOR," they say. However, they note that the trials "had smaller sample sizes [approximately 1000 patients each], used only 25% of the dose of rofecoxib used in VIGOR, and had few events for meaningful comparison. Thus the prothrombotic effect seen with rofecoxib may potentially be dose dependent."
The authors also searched the FDA Adverse Event Reporting System in 2001 and found that 99 thrombotic or embolic events had been attributed to rofecoxib and 102 to celecoxib in the US., 百拇医药