Celecoxib, ibuprofen, and the antiplatelet effect of aspirin in patients with osteoarthritis and ischemic heart disease

Clin Pharmacol Ther. 2006 Sep;80(3):264-74. doi: 10.1016/j.clpt.2006.05.004.


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 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Aged
  • Arachidonic Acid / pharmacology
  • Aspirin / administration & dosage
  • Aspirin / therapeutic use*
  • Aspirin / urine
  • Celecoxib
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Ibuprofen / administration & dosage
  • Ibuprofen / therapeutic use*
  • Ibuprofen / urine
  • Male
  • Middle Aged
  • Myocardial Ischemia / blood
  • Myocardial Ischemia / drug therapy*
  • Osteoarthritis / blood
  • Osteoarthritis / drug therapy*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / therapeutic use
  • Platelet Aggregation Inhibitors / urine
  • Platelet Function Tests / methods
  • Pyrazoles / administration & dosage
  • Pyrazoles / therapeutic use*
  • Pyrazoles / urine
  • Sulfonamides / administration & dosage
  • Sulfonamides / therapeutic use*
  • Sulfonamides / urine
  • Thromboxane B2 / analogs & derivatives
  • Thromboxane B2 / blood
  • Thromboxane B2 / urine
  • Treatment Outcome


  • Platelet Aggregation Inhibitors
  • Pyrazoles
  • Sulfonamides
  • Arachidonic Acid
  • Thromboxane B2
  • Adenosine Diphosphate
  • 11-dehydro-thromboxane B2
  • Celecoxib
  • Aspirin
  • Ibuprofen