Celecoxib, ibuprofen, and the antiplatelet effect of aspirin in patients with osteoarthritis and ischemic heart disease.
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 B(2) (TXB(2)) levels, as well as platelet function. In contrast, a significant (P < .001) increase in serum TXB(2) 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-TXB(2), 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 E(2) generation, a marker of COX-2 activity ex vivo, was caused by ibuprofen (>or=80%) or celecoxib (>or=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.
Renda
Giulia
G
Departments of Medicine and Clinical Sciences, Center of Excellence on Aging, G. d'Annunzio University, School of Medicine, Chiete, Italy.
Tacconelli
Stefania
S
Capone
Marta L
ML
Sacchetta
Daniele
D
Santarelli
Francesco
F
Sciulli
Maria G
MG
Zimarino
Marco
M
Grana
Marilena
M
D'Amelio
Elisabetta
E
Zurro
Maria
M
Price
Thomas S
TS
Patrono
Carlo
C
De Caterina
Raffaele
R
Patrignani
Paola
P
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use* / Q000652:urine; D000068579:Celecoxib; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000627:therapeutic use* / Q000652:urine; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000188:drug therapy*; D010003:Osteoarthritis / Q000097:blood / Q000188:drug therapy*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use / Q000652:urine; D010979:Platelet Function Tests / Q000379:methods; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use* / Q000652:urine; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use* / Q000652:urine; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D016718:Arachidonic Acid; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; C049235:11-dehydro-thromboxane B2; D000068579:Celecoxib; D001241:Aspirin; D007052:Ibuprofen