NEW YORK (Reuters Health) - Treatment with S18886, an experimental thromboxane receptor antagonist, slows plaque progression in a murine model of atherosclerosis, new research shows. While co-treatment with a COX-2 inhibitor might be expected to enhance this effect, such therapy actually seems to undermine plaque stability.
This finding could help explain recent reports linking COX-2 inhibitors with an increased risk of heart disease and stroke, the researchers note in the January 17th issue of Circulation: Journal of the American Heart Association. The results may be particularly relevant for patients adding a COX-2 inhibitor to aspirin, a drug that blocks thromboxane formation and thus may act like S18886.
In September, Merck & Co. Inc. pulled its COX-2 inhibitor Vioxx from the market after the drug was linked to an increased risk of MI. And in December, the National Institutes of Health halted a study involving Pfizer’s COX-2 inhibitor Celebrex.
However, results from a meta-analysis, also reported in Circulation, indicate that the elevated risks are not confined to these older COX-2 inhibitors. Indeed, Pfizer’s newer drug Bextra (valdecoxib) tripled the risk of cardiovascular events compared with placebo.
Dr. Garret A. FitzGerald, from the University of Pennsylvania in Philadelphia, and colleagues, conducted the experimental study and the meta-analysis.
In the lab study, atherosclerosis-prone mice were treated with S18886, indomethacin, or an experimental COX-2 inhibitor called MF tricyclic. As noted, S18886 retarded atherogenesis in the animals, whereas indomethacin, an inhibitor of both COX-1 and COX-2, as well as MF tricyclic did not produce this effect.
Given the nature of the cyclooxygenase pathway, one might expect a further slowing of atherogenesis when S18886 is given with MF tricyclic. Instead, the investigators found evidence that the COX-2 inhibitor promoted plaque destabilization when used with this agent.
“These results would have disturbing implications for patients at high cardiovascular risk treated with aspirin and a (COX-2 inhibitor),” Dr. FitzGerald said in a statement.
The US Food and Drug Administration has cautioned patients to limit their use of COX-2 inhibitors and will hold a meeting next month to discuss them. The European Medicines Agency is holding a similar meeting this week.
Source: Circulation 2005;111. [ Google search on this article ]
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