Thrombosis rofecoxib

Selective inhibitors of COX-2 are thought to be problematic in this regard. They depress PGf formation by endothelial cells without concomitant inhibition of platelet thromboxane. PGf restrains the cardiovascular effects of TXA2, affording a mechanism by which selective inhibitors might increase the risk of thrombosis consistent with results from postmarketing trials of rofecoxib. 

This mechanism should pertain to individuals otherwise at risk of thrombosis, such as those with rheumatoid arthritis, as the relative risk of myocardial infarction is increased in these patients compared to patients with osteoarthritis or no arthritis. The incidence of myocardial infarction and stroke has diverged in such at-risk patients when COX-2 inhibitors are compared with tNSAIDs. Placebo-controlled trials have now revealed an increased incidence of myocardial infarction and stroke in patients treated with rofecoxib, valdecoxib, and celecoxib, consistent with a mechanism-based cardiovascular hazard for the class. Regulatory agencies in the U.S., Europe, and Australia have concluded that all three drugs increase the risk of heart attack and stroke and will be labeled accordingly and restricted with respect to marketing directly to consumers. Only celecoxib remains on the market in the U.S. 

The first COX-2 inhibitor approved by the US Food and Drug Administration (FDA) in 1998 was celecoxib (Celebrex). This was soon followed by the approval of rofecoxib (Vioxx) and valdecoxib (Bex-tra). Since then, valdecoxib and rofecoxib have both been voluntarily withdrawn from the US market because of an increased stroke and cardiovascular risk, especially that of thrombosis. Currently, celecoxib is the only COX-2 inhibitor available in the... 

Observational studies In postmarketing surveillance of serious adverse events associated with the use of rofecoxib from 1999 to 2002 there were 31 024 reports of serious adverse events, and the drug was considered the primary suspect in 97.8% of reports [51 ]. There were 3915, 3677, 1653, 1917, and 233 reports of hemorrhage, edema, death, thrombosis, and embolism respectively. The authors argued that, in addition to the risk of myocardial infarction and stroke, rofecoxib use might be associated with an increased risk of hemorrhage. A limitation of this analysis was that the data may have contained multiple reports from the same individual. 

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