¹Departments of Medicine and Clinical Sciences and Bioimaging and Center of Excellence on Aging, "G. d'Annunzio" University, School of Medicine, and "Gabriele d'Annunzio" University Foundation, Chieti; Department of Pharmacology, University of Rome "La Sapienza," 2nd School of Medicine, Rome; and Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia

Correspondence: Paola Patrignani, PhD, Sezione di Farmacologia, Dipartimento di Medicina e Scienze dell'Invecchiamento, Università di Chieti "G. d'Annunzio," Via dei Vestini, 31, 66013 Chieti, Italy E-mail: ppatrignani@unich.it

^*Supported by grants from Pfizer, Rome, Italy, and from the Italian Ministry of University and Research (MIUR) to Dr Patrignani. (FIRB).

Received 22 November 2005; Accepted 3 May 2006.

Abstract

Background and Objective: We performed a placebo-controlled, randomized study to address whether celecoxib or ibuprofen undermines the functional range of inhibition of platelet cyclooxygenase (COX)–1 activity by aspirin in patients with osteoarthritis and stable ischemic heart disease.

Methods: Twenty-four patients who were undergoing long-term treatment with aspirin (100 mg daily) for cardioprotection were coadministered celecoxib, 200 mg twice daily, ibuprofen, 600 mg 3 times daily, or placebo for 7 days.

Results: The coadministration of placebo or celecoxib did not undermine the aspirin-related inhibition of platelet COX-1 activity, as assessed by measurements of serum thromboxane B₂ (TXB₂) levels, as well as platelet function. In contrast, a significant (P < .001) increase in serum TXB₂ level was detected on day 7 before drug administration (median, 19.13 ng/mL [range, 1-47.5 ng/mL]) and at 24 hours after the coadministration of aspirin and ibuprofen (median, 22.28 ng/mL [range, 4.9-44.4 ng/mL]) versus baseline (median, 1.65 ng/mL [range, 0.55-79.8 ng/mL]); this was associated with a significant increase in arachidonic acid–induced platelet aggregation (P < .01) and adenosine diphosphate–induced platelet aggregation (P < .05) and a decrease in the time to form an occlusive thrombus in the platelet function analyzer (P < .01). The urinary excretion of 11-dehydro-TXB₂, an index of systemic thromboxane biosynthesis, was not significantly affected by the coadministration of treatment drugs. At steady state, a comparable and persistent inhibition of lipopolysaccharide-stimulated prostaglandin E₂ generation, a marker of COX-2 activity ex vivo, was caused by ibuprofen (80%) or celecoxib (70%) but not placebo.

Conclusions: Unlike ibuprofen, celecoxib did not interfere with the inhibition of platelet COX-1 activity and function by aspirin despite a comparable suppression of COX-2 ex vivo in patients with osteoarthritis and stable ischemic heart disease.