Korean Circ J.  2010 Jul;40(7):321-327. 10.4070/kcj.2010.40.7.321.

Celecoxib Does Not Attenuate the Antiplatelet Effects of Aspirin and Clopidogrel in Healthy Volunteers

• Lee W
• Suh JW
• Yang HM
• Kwon DA
• Cho HJ
• Kang HJ
• Kim HS
• Oh BH

• KMID: 2225175
• DOI: http://doi.org/10.4070/kcj.2010.40.7.321

Abstract

BACKGROUND AND OBJECTIVES
The prevalence of arthritis, which is often treated with celecoxib, is high in patients with coronary artery disease. Furthermore, celecoxib has been reported to reduce restenosis after coronary stenting by inhibiting expression of the proto-oncogene Akt. A concern is that celecoxib increases thrombogenicity by inhibiting the synthesis of prostacyclin in endothelial cells. However, it is not known whether the administration of celecoxib will attenuate the antiplatelet effects of aspirin and clopidogrel, which are used after stenting. We addressed this gap in our knowledge.
SUBJECTS AND METHODS
We recruited healthy volunteers (n=40) and randomized them into five subgroups (n=8 for each group: aspirin, celecoxib, aspirin+celecoxib, aspirin+clopidogrel, and aspirin+clopidogrel+celecoxib). Each subject received their medications for 6 days and blood samples were taken on day 0 and day 7. Celecoxib (200 mg twice a day), and/or aspirin (100 mg daily), and/or clopidogrel (75 mg daily) were administered. We compared platelet function among subgroups using light transmittance aggregometry and arachidonic acid metabolite assays.
RESULTS
Celecoxib treatment alone did not significantly affect platelet aggregation. The reduction in adenosine diphosphase (ADP)-induced platelet aggregation by aspirin+clopidogrel was not affected by addition of celecoxib (31.3+/-6.9% vs. 32.4+/-12.2%, p=0.83). Inhibition of collagen-induced platelet aggregation by aspirin+clopidogrel was not affected by addition of celecoxib (47.6+/-13.4% vs. 51.6+/-3.7%, p=0.69). Drug-induced changes in prostacyclin and thromboxane levels did not differ among treatment groups.
CONCLUSION
Celecoxib treatment does not interfere with the antiplatelet effects of aspirin or clopidogrel, suggesting that celecoxib can be safely administered in combination with dual antiplatelet therapy in patients with coronary stenting without increased thrombogenicity.

Keyword

Celecoxib; Platelet aggregation inhibitors; Thrombosis

MeSH Terms

Adenosine
Arachidonic Acid
Arthritis
Aspirin
Blood Platelets
Coronary Artery Disease
Endothelial Cells
Epoprostenol
Humans
Light
Platelet Aggregation
Platelet Aggregation Inhibitors
Prevalence
Proto-Oncogenes
Pyrazoles
Stents
Sulfonamides
Thrombosis
Celecoxib
Ticlopidine
Adenosine
Arachidonic Acid
Aspirin
Epoprostenol
Platelet Aggregation Inhibitors
Pyrazoles
Sulfonamides
Ticlopidine

Figure

• 

  Fig. 1 Platelet aggregation (%) induced by (A) ADP, and (B) collagen. Platelet aggregation was measured on day 0 (Pre), and day 7 (Post). Values are means±standard deviation. *p<0.05. ADP: adenosine 5'-diphosphate, CCX: celecoxib, ASA: aspirin, CPD: clopidogrel, Pre: pretreatment, post: post-treatment.

• 

  Fig. 2 Reductions in platelet aggregation (Pretreatment inhibition %-Post-treatment inhibition %) by antiplatelet agents with or without addition of celecoxib. A: comparison between aspirin (ASA) and aspirin+celecoxib (ASA+CCX). B: comparison between aspirin+clopidogrel group (ASA+CPD) and aspirin+clopidogrel+celecoxib (ASA+CPD+CCX). Values are means±standard deviation. *p<0.05. ADP: adenosine 5'-diphosphate.

• 

  Fig. 3 Effects of celecoxib, aspirin, and clopidogrel on the production of prostacyclin and thromboxane B2. Urinary excretion of 6-keto PGF1α (pg/mg creatinine) and 11-dehydro TXB2 (pg/mg creatinine) were measured before and after each Treatment. A: celecoxib (CCX), B: aspirin (ASA), C: aspirin+celecoxib (ASA+CCX), D: aspirin+clopidogrel (ASA+CPD), E: aspirin+clopidogrel+celecoxib (ASA+CCX+CPD). Values are means±standard deviation. *p<0.05. Pre: pre-treatment, Post: post-treatment.

• 

  Fig. 4 Effects of celecoxib on the production of prostacyclin and thromboxane B2 in combination with antiplatelet agents. The height of bars represents changes (post-treatment-pre-treatment) of (A) urinary 6-keto PGF1α levels (pg/mg creatinine) and (B) 11-dehydro TXB2 levels (pg/mg creatinine). Values are means±standard deviation. *p<0.05. CCX: celecoxib, ASA: aspirin, CPD: clopidogrel.

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