Daily administration of the TP receptor antagonist terutroban improved endothelial function in high-cardiovascular-risk patients with atherosclerosis

What is already known about this subject: • Terutroban is a selective TP receptor antagonist, i.e. a specific antagonist of the thromboxane A(2) and prostaglandin endoperoxide receptors, shown to improve endothelial function after a single administration in patients with coronary artery disease.

What this study adds: • This randomized, double-blind, placebo-controlled trial demonstrates that repeated-dose terutroban for 15 days improves endothelial function and inhibits thromboxane A(2) -induced platelet aggregation in high-cardiovascular-risk patients taking 300 mg of aspirin per day. Terutroban may prove useful for preventing cardiovascular events in such patients.

Aims: The specific TP receptor antagonist terutroban improves endothelial function after a single dose in patients with coronary artery disease. Our aim was to evaluate the effects and dose dependency of repeated-dose terutroban on endothelial function and platelet aggregation in high-cardiovascular-risk patients with carotid atherosclerosis.

Methods: We randomly allocated 48 patients taking 300 mg aspirin per day to placebo or to one of three terutroban dosages (2.5, 5 or 10 mg) for 15 days in a double-blind study. Flow-mediated vasodilatation was evaluated before and 2 h after the first oral dose on day 0 and 2 h after the last oral dose on day 14.

Results: On day 0 and day 14, all three terutroban dosages improved flow-mediated vasodilatation and abolished platelet aggregation induced by the TP receptor agonist U46619, without changing the aggregation response to ADP or Collagen.

Conclusion: Terutroban, by chronically improving endothelium-dependent vasodilatation and inhibiting platelet aggregation, may prove useful for preventing cardiovascular events in high-risk patients.