Comments on: http://www.kevinmd.com/blog/2005/11/third-vioxx-trial-it-didnt-matter-what.html Wed, 15 Feb 2012 00:27:00 +0000 hourly 1 By: Anonymoushttp://www.kevinmd.com/blog/2005/11/third-vioxx-trial-it-didnt-matter-what.html#comment-57275 Anonymous Wed, 30 Nov 2005 16:46:00 +0000 http://clients.emmense.com/kevinmd/2005/11/19481.html#comment-57275 How Vioxx causes thrombosis:<br/><br/>"Thromboxane A2, a major COX-1–mediated product of arachidonic acid metabolism, causes irreversible platelet aggregation, vasoconstriction, and smooth-muscle proliferation, whereas prostacyclin is an inhibitor of platelet aggregation, a vasodilator, and an inhibitor of smooth-muscle proliferation. COX-2 is the chief source of systemic prostacyclin synthesis, and COX-2 inhibitors may increase the cardiovascular risk by shifting the functional balance of these vasoactive eicosanoids toward the promotion of thrombosis or atherogenesis. COX-2 inhibition combined with thromboxane-receptor antagonism may also lead to the destabilization of atheromatous plaque. In addition, COX-2 plays a role in angiogenesis. How these pharmacologic observations relate to the clinical cardiovascular findings with COX-2 inhibition is unknown." -NEJM, March 17, 2005,Cardiovascular Events Associated with Rofecoxib... How Vioxx causes thrombosis:

“Thromboxane A2, a major COX-1–mediated product of arachidonic acid metabolism, causes irreversible platelet aggregation, vasoconstriction, and smooth-muscle proliferation, whereas prostacyclin is an inhibitor of platelet aggregation, a vasodilator, and an inhibitor of smooth-muscle proliferation. COX-2 is the chief source of systemic prostacyclin synthesis, and COX-2 inhibitors may increase the cardiovascular risk by shifting the functional balance of these vasoactive eicosanoids toward the promotion of thrombosis or atherogenesis. COX-2 inhibition combined with thromboxane-receptor antagonism may also lead to the destabilization of atheromatous plaque. In addition, COX-2 plays a role in angiogenesis. How these pharmacologic observations relate to the clinical cardiovascular findings with COX-2 inhibition is unknown.” -NEJM, March 17, 2005,Cardiovascular Events Associated with Rofecoxib…

]]> By: gghttp://www.kevinmd.com/blog/2005/11/third-vioxx-trial-it-didnt-matter-what.html#comment-57273 gg Wed, 30 Nov 2005 16:26:00 +0000 http://clients.emmense.com/kevinmd/2005/11/19481.html#comment-57273 Do we know the mechanism by which Vioxx increases risk of heart attacks? If it simply increases thrombosis in the short term, it is quite possible the risk occurs soon after the drug is started. Remeber, the studies showed a significant difference AT a number of months, meaning the events tallied all occured BEFORE that time. Some of the events may have occured in the first month, but the difference was not enough to be statistically significant. Perhaps if we looked at a larger sample... Of course even with the increased risk, its ridiculous to assign 100% of the blame for this heart attack to a single drug, when he had other factors increasing risk (age, male sex, 60% blockage). Do we know the mechanism by which Vioxx increases risk of heart attacks? If it simply increases thrombosis in the short term, it is quite possible the risk occurs soon after the drug is started. Remeber, the studies showed a significant difference AT a number of months, meaning the events tallied all occured BEFORE that time. Some of the events may have occured in the first month, but the difference was not enough to be statistically significant. Perhaps if we looked at a larger sample… Of course even with the increased risk, its ridiculous to assign 100% of the blame for this heart attack to a single drug, when he had other factors increasing risk (age, male sex, 60% blockage).

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