Cyclooxygenase-2 inhibition and coagulation.
Selective inhibitors of cyclooxygenase-2 (COX-2) have come under scrutiny because of a possibly increased thrombotic risk observed in retrospective studies and comparatively small cancer trials. Indeed, inhibition of COX-2 may favor a prothrombotic environment by suppressing endothelial prostacyclin synthesis while leaving COX-1-dependent platelet thromboxane (TX) A2 synthesis unopposed. However, in vitro studies have shown that the effect of coxibs on coagulation is dependent on several variables; for example, the coxib celecoxib reduces endothelial tissue factor expression, a key initiator of the coagulation cascade. Furthermore, animal studies are inconclusive as some studies investigating the effect of COX-2 inhibition in atherosclerosis imply a detrimental effect of coxibs, whereas others suggest a beneficial effect on plaque progression and stability. In healthy human subjects and in patients with atherosclerotic vascular diseases, the effect of COX-2 inhibition on coagulation is equally unclear as no prospective, randomized, double-blinded studies sufficiently powered to investigate cardiovascular endpoints have been performed to directly investigate a potentially cardiotoxic effect of coxibs. Here, we review the effect of COX-2 inhibition on the coagulation system; we discuss the molecular mechanisms involved and summarize important clinical trials in which an increased frequency of thrombotic complications coxibs was observed.
Steffel
Jan
J
Cardiovascular Research, Physiology Institute, University of Zürich, and Cardiology, Cardiovascular Center, University Hospital Zürich, Zürich, Switzerland.
Lüscher
Thomas F
TF
Ruschitzka
Frank
F
Tanner
Felix C
FC
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D023421:Models, Animal
D016861:Cyclooxygenase Inhibitors; D051546:Cyclooxygenase 2