Optimal suppression of thromboxane a2 formation by aspirin during percutaneous transluminal coronary angioplasty: no additional effect of a selective cyclooxygenase-2 inhibitor Original Research Article

Objectives We examined the contribution of cyclooxygenase (COX)-1 and -2 to the generation of prostacyclin, thromboxane (Tx) A2, and 8-epi prostaglandin (PG) F2α during percutaneous transluminal coronary angioplasty (PTCA). Background Both TxA2 and 8-epi PGF2α activate platelets and are mitogenic, whereas prostacyclin is a platelet inhibitor, and therefore may influence the outcome of PTCA. Methods Twenty-one patients undergoing PTCA while receiving aspirin 300 mg daily or aspirin plus the selective COX-2 inhibitor nimesulide were compared with 13 patients treated only with fradafiban, a glycoprotein IIb/IIIa antagonist. Urine was analyzed for the metabolites of TxA2 (Tx-M) and prostacyclin (PGI-M) and for the isoprostane, 8-epi PGF2α. Results In the fradafiban group, there was a marked increase in Tx-M during PTCA (mean, 1,973; 95% confidence interval [CI] 112 to 3,834 rising to mean 7,645; 95% CI 2,009 to 13,281 pg/mg creatinine, P = 0.018). The Tx-M excretion was similarly reduced by aspirin and the combination of aspirin and nimesulide. In contrast, the combination of nimesulide and aspirin inhibited PGI-M excretion to a greater extent than aspirin (p = 0.001). Urinary 8-epi PGF2α excretion was elevated following PTCA compared with normal subjects (p = 0.002) and appeared to be unaffected by any of the treatments. Conclusions The increase in TxA2 during PTCA is primarily COX-1 dependent, and aspirin alone is effective in suppressing its formation. In contrast, prostacyclin generation is both COX-1 and COX-2 dependent. The inhibition of COX-1 and COX-2 did not prevent the production of 8-epi PGF2α, suggesting that this is not enzymatically derived. The persistent generation of 8-epi PGF2α may contribute to the thrombosis and restenosis that complicate PTCA.