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

Abstract

Background and ObjectivesThe 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 MethodsWe 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.ResultsCelecoxib 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.ConclusionCelecoxib 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.

Safe prescribing of non-steroidal anti-inflammatory drugs in patients with osteoarthritis – an expert consensus addressing benefits as well as gastrointestinal and cardiovascular risks

“…COX-2 selective NSAIDs spare platelet COX-1 activity [ 198 ] and do not affect platelet aggregation [ 184 , 198 - 201 ] or bleeding time [ 200 ]. Similarly, COX-2 selective inhibitors do not interfere with the anti-aggregant activity of low-dose aspirin both in healthy subjects [ 184 , 186 , 187 , 198 ] and patients with coronary heart disease [ 202 , 203 ]. Consistent with these results, in vitro studies on human platelets have shown that a low affinity for COX-1 and a high degree of COX-2 selectivity confers a low potential to block aspirin inhibition of platelet COX-1 [ 204 ].…”

“…Indeed, the vascular effects of celecoxib 200 mg daily (the most widely used regimen) were statistically uncertain. In contrast to ns-NSAIDs, celecoxib does not impair the antiplatelet activity of low-dose aspirin, either alone [ 187 , 202 ] or in combination with clopidogrel [ 203 ]. This lack of interference with the antithrombotic action of antiplatelet drugs would make this COX-2 selective agent a suitable anti-inflammatory drug for patients receiving low-dose aspirin for CV or cerebrovascular prevention [ 205 ], despite the contrary opinion of the EMA [ 206 ].…”

Comparative Risks of Nonsteroidal Anti‐inflammatory Drugs on Cardiovascular Diseases: A Population‐Based Cohort Study

“…28 It has been postulated that the antiplatelet activity of aspirin can be attenuated by some NSAIDs 36,37 but not celecoxib. [37][38][39] This could possibly explain why they achieved different results in a population of post-MI patients who were taking antiplatelet drugs, whereas only 2.0% of the NSAID users in the current study were taking aspirin. 28 While evidence from observational studies remains inconclusive, prior randomized controlled trials also did not reveal a difference in CV outcomes between celecoxib, naproxen, and ibuprofen, 40,41 which is consistent with our findings.…”

“…In the Korean cohort study, since only patients who were first diagnosed with MI were included, most of them were on antiplatelet or anticoagulation therapy 28 . It has been postulated that the antiplatelet activity of aspirin can be attenuated by some NSAIDs 36,37 but not celecoxib 37‐39 . This could possibly explain why they achieved different results in a population of post‐MI patients who were taking antiplatelet drugs, whereas only 2.0% of the NSAID users in the current study were taking aspirin 28 .…”

Cardiovascular Safety of Celecoxib on Top of Dual Antiplatelet Therapy

“…In the current review, Lee et al 10) assessed whether celecoxib therapy would negate the antiplatelet effects of aspirin and clipidogrel in healthy, young-aged volunteers using light transmittance aggregometry and arachidonic acid metabolite assay. Volunteers were divided into 5 groups (n=8 per group) by treatment regimen that included aspirin (100 mg/d), clopidogrel (75 mg/d) and celecoxib (400 mg/d): aspirin; celecoxib; asprin+celecoxib; aspirin+clopidogrel; and aspirin+clopidogrel+celecoxib.…”