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Arterioscler. Thromb. Vasc. Biol. · Jun 2003
Randomized Controlled Trial Comparative Study Clinical TrialEffects of cyclooxygenases inhibitors on vasoactive prostanoids and thrombin generation at the site of microvascular injury in healthy men.
- Ewa Tuleja, Filip Mejza, Adam Cmiel, and Andrzej Szczeklik.
- Department of Medicine, Jagiellonian University School of Medicine, Cracow, Poland.
- Arterioscler. Thromb. Vasc. Biol. 2003 Jun 1; 23 (6): 1111-5.
ObjectiveBalance between vasoactive prostanoids that contribute to homeostasis of the circulatory system can be affected by cyclooxygenases inhibitors. Results of a recent large clinical trial show that myocardial infarction was more frequent among patients with rheumatoid arthritis treated with the selective cyclooxygenase-2 inhibitor rofecoxib compared with those treated with naproxen. Whether this difference was attributable to deleterious cardiovascular effects of rofecoxib or cardioprotective effects of naproxen has not been determined. We tested the hypothesis that naproxen, contrary to rofecoxib, exerts antithrombotic effects.Methods And ResultsForty-five healthy men were randomized to receive a 7-day treatment with rofecoxib (50 mg/d), naproxen (1000 mg/d), aspirin (75 mg/d), or diclofenac (150 mg/d). Formation of thromboxane, prostacyclin, and thrombin in the bleeding-time blood at the site of standardized microvascular injury was assessed before and after treatment. Naproxen, like aspirin, caused significant reduction of both thromboxane and prostacyclin, whereas diclofenac depressed prostacyclin synthesis but had no effect on tromboxane formation. Naproxen and aspirin significantly suppressed thrombin generation. Diclofenac showed a similar tendency, which did not reach statistical significance. Rofecoxib had no effect on any variables measured.ConclusionsIn healthy men, naproxen exerts an antithrombotic effect at least as potent as aspirin, whereas rofecoxib does not affect hemostatic balance.
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