The Antiplatelet Effect of Six Non-Steroidal Anti-Inflammatory Drugs and Their Pharmacodynamic Interaction With Aspirin in Healthy Volunteers

Gladding, Patrick; Webster, Mark; Farrell, Helen; Zeng, Irene; Park, Robert; Ruijne, Nicola

doi:10.1016/j.amjcard.2007.11.054

Cited by 136 publications

(102 citation statements)

References 20 publications

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“…Aspirin is widely used in conjunction with Celebrex to attenuate the cardiovascular side effects of COX-2 inhibitors (6,15,16,19). Studies in humans have suggested that celecoxib does not interfere with the effect of a conventional aspirin tablet containing 324 mg of aspirin (15,16).…”

Section: Discussionmentioning

confidence: 99%

“…Studies in humans have suggested that celecoxib does not interfere with the effect of a conventional aspirin tablet containing 324 mg of aspirin (15,16). However, what is generally considered to be low-dose aspirin (i.e., 81 mg), which is metabolized rapidly to an ineffective concentration, has not been tested vs. celecoxib.…”

Section: Discussionmentioning

confidence: 99%

“…This suggests that COX-2 inhibitors are able to bind to COX-1 and somehow compete with nsNSAID actions on COX-1 without affecting AA oxygenation. This is a potentially important clinical issue because many elderly patients take a combination of a coxib for pain relief and low-dose aspirin to counterbalance the potential cardiovascular side effects of coxibs (6,15,16).…”

mentioning

confidence: 99%

“…Extensive clinical trial data on interactions between aspirin and coxibs are only available for one coxib, rofecoxib (16)(17)(18)(19), and no significant effect on aspirin inhibition of thrombosis was detected. However, rofecoxib is the COX-2 inhibitor that is least effective in attenuating aspirin inhibition of COX-1 in vitro (14).…”

mentioning

confidence: 99%

“…Currently, the most widely used coxib is celecoxib. In two small trials with healthy human volunteers, the effects of aspirin were found not to be attenuated by celecoxib (15,16); however, in both trials, the volunteers were given a 324 mg daily dose of aspirin, which is four times the dose of 81 mg commonly considered to be "low-dose" aspirin. In a potentially related study, celecoxib did attenuate aspirin inhibition in a dog model of thrombosis (20).…”

mentioning

confidence: 99%

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Coxibs interfere with the action of aspirin by binding tightly to one monomer of cyclooxygenase-1

Rimon

Sidhu

Lauver

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

168

210

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Pain associated with inflammation involves prostaglandins synthesized from arachidonic acid (AA) through cyclooxygenase-2 (COX-2) pathways while thromboxane A 2 formed by platelets from AA via cyclooxygenase-1 (COX-1) mediates thrombosis. COX-1 and COX-2 are both targets of nonselective nonsteroidal antiinflammatory drugs (nsNSAIDs) including aspirin whereas COX-2 activity is preferentially blocked by COX-2 inhibitors called coxibs. COXs are homodimers composed of identical subunits, but we have shown that only one subunit is active at a time during catalysis; moreover, many nsNSAIDS bind to a single subunit of a COX dimer to inhibit the COX activity of the entire dimer. Here, we report the surprising observation that celecoxib and other coxibs bind tightly to a subunit of COX-1. Although celecoxib binding to one monomer of COX-1 does not affect the normal catalytic processing of AA by the second, partner subunit, celecoxib does interfere with the inhibition of COX-1 by aspirin in vitro. X-ray crystallographic results obtained with a celecoxib/COX-1 complex show how celecoxib can bind to one of the two available COX sites of the COX-1 dimer. Finally, we find that administration of celecoxib to dogs interferes with the ability of a low dose of aspirin to inhibit AA-induced ex vivo platelet aggregation. COX-2 inhibitors such as celecoxib are widely used for pain relief. Because coxibs exhibit cardiovascular side effects, they are often prescribed in combination with low-dose aspirin to prevent thrombosis. Our studies predict that the cardioprotective effect of low-dose aspirin on COX-1 may be blunted when taken with coxibs.arachidonic acid | adrenic acid | nonsteroidal antiinflammatory drugs | platelet | prostaglandin

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Coxibs interfere with the action of aspirin by binding tightly to one monomer of cyclooxygenase-1

Rimon

Sidhu

Lauver

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

168

210

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Use of nonsteroidal anti-inflammatory drugs in the older adult

Fowler

Durham

Planton

et al. 2014

Journal of the American Association of Nurse Practitioners

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Purpose Annually, approximately 90 million prescriptions are filled for nonsteroidal anti‐inflammatory drugs (NSAIDs) with the number prescribed for older adults approximately three times higher than for younger adults. This article examines the benefits and risk of NSAID use in older adults. Data sources Electronic data collection of research studies, evidence‐based reviews, consensus statements, and guidelines related to the purpose of this article were analyzed if published between 2000 and 2013 in English from Ovid, MEDLINE, and PubMed databases. Conclusions While NSAIDs are commonly used to treat pain and inflammation in older adults, strong consideration must be given to the potential adverse effects. A lack of consistency in the guidelines regarding NSAID use poses further challenges for clinicians in the selection of the best pharmacological approach. When prescribing NSAIDs, adverse events, polypharmacy, comorbidities, and treatment guidelines must be considered. NSAIDs are an appropriate option for pain management in select older adults, often after a trial of acetaminophen and if benefits outweigh risks. Alternative pharmacological and nonpharmacological therapies may be more appropriate in many older adults. Implications for practice The challenge for clinicians prescribing NSAIDs in the treatment of pain in older adults is to utilize safe, individualized, and evidenced‐based pain management regimens.

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Cardiovascular Toxicities of NSAIDS: Epidemiologic Aspects

González‐Pérez

Rodrı́guez

2010

Cardiotoxicity of Non‐Cardiovascular Drugs

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The Antiplatelet Effect of Six Non-Steroidal Anti-Inflammatory Drugs and Their Pharmacodynamic Interaction With Aspirin in Healthy Volunteers

Cited by 136 publications

References 20 publications

Coxibs interfere with the action of aspirin by binding tightly to one monomer of cyclooxygenase-1

Coxibs interfere with the action of aspirin by binding tightly to one monomer of cyclooxygenase-1

Use of nonsteroidal anti-inflammatory drugs in the older adult

Cardiovascular Toxicities of NSAIDS: Epidemiologic Aspects

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