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CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY

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

Dermot Kearney, MD^*, Anthony Byrne, MD^*, Peter Crean, MD, FRCPI, Dermot Cox, PhD^* and Desmond J. Fitzgerald, MD, FRCPI^*,*

^* Department of Clinical Pharmacology, RCSI, Dublin, Ireland
Department of Cardiology, St. James' Hospital, Dublin, Ireland

Manuscript received January 19, 2003; revised manuscript received September 22, 2003, accepted September 26, 2003.

^* Reprint requests and correspondence: Prof. Desmond J. Fitzgerald, Dept. of Clinical Pharmacology, Royal College of Surgeons in Ireland, 123, St. Stephen's Green, Dublin 2, Ireland.
dfitzgerald{at}rcsi.ie

OBJECTIVES: We examined the contribution of cyclooxygenase (COX)-1 and -2 to the generation of prostacyclin, thromboxane (Tx) A₂, and 8-epi prostaglandin (PG) F₂ during percutaneous transluminal coronary angioplasty (PTCA).

BACKGROUND: Both TxA₂ and 8-epi PGF₂ 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 PGF₂.

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 PGF₂ 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 PGF₂, suggesting that this is not enzymatically derived. The persistent generation of 8-epi PGF₂ may contribute to the thrombosis and restenosis that complicate PTCA.

Abbreviations and Acronyms   COX = cyclooxygenase   GP = glycoprotein   MI = myocardial infarction   NSAID = non-steroidal anti-inflammatory drug   PG = prostaglandin   PGI2 = prostacyclin   PGI-M = 2,3 dinor-6-keto-PGF1   PTCA = percutaneous transluminal coronary angioplasty   Tx = thromboxane   Tx-M = 11-dehydro-TxB2

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