Why Are Some Individuals Resistant to the Cardioprotective Effects of Aspirin?

Halushka, Marc K.; Halushka, Perry V.

doi:10.1161/01.cir.0000015422.86569.52

Cited by 101 publications

(71 citation statements)

References 24 publications

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“…The following potential mechanisms could be considered responsible for "true" aspirin resistance: (1) decreased bioavalaibility of aspirin; (2) competition of aspirin with other NSAIDs (such as ibuprofen) preventing aspirin access at Ser530 of COX-1; 66 (3) accelerated platelet turnover, introducing newly formed, nonaspirinated platelets into blood stream; 39 (4) transcellular formation of TxA 2 by aspirinated platelets from PGH 2 released by other blood cells or vascular cells; 68,74 (5) TxA 2 production by the aspirin-insensitive COX-2 in newly formed platelets or other cells; 3,68 and (6) (theoretical) presence of variant COX-1 that is less responsive to aspirin inhibition. 68 In patients undergoing coronary artery bypass surgery, Zimmerman et al showed that aspirin inhibition of TxA 2 biosynthesis both in vitro and ex vivo is compromised within several days after surgery.…”

Section: True Aspirin Resistancementioning

confidence: 99%

“…68 In patients undergoing coronary artery bypass surgery, Zimmerman et al showed that aspirin inhibition of TxA 2 biosynthesis both in vitro and ex vivo is compromised within several days after surgery. 4 Despite the fact that immunoreactive COX-2 in platelets was increased 16-fold, it appeared not to be responsible for aspirin resistance, because a specific COX-2 inhibitor did not affect TxA 2 production.…”

Section: True Aspirin Resistancementioning

confidence: 99%

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Aspirin and Clopidogrel

Cattaneo

2004

ATVB

371

133

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Abstract-Aspirin and the thienopyridines ticlopidine and clopidogrel are antiplatelet agents that display good antithrombotic activity. In the past few years, the concept of aspirin resistance has been largely emphasized in the medical literature, although its definition is still uncertain. I suggest that "aspirin-resistant" should be considered as a description for those individuals in whom aspirin fails to inhibit thromboxane A 2 production, irrespective of the results of unspecific tests of platelet function, such as the bleeding time, platelet aggregation, or the PFA-100 system. Less well known than aspirin resistance, but certainly better characterized, is the issue of "clopidogrel resistance," which is probably mostly caused by inefficient metabolism of the prodrug clopidogrel to its active metabolite. At present, aspirin and clopidogrel resistance should not be looked for in the clinical setting, because there is no definite demonstration of an association with clinical events conditioning cost-effective changes in patient management. Key Words: aspirin resistance Ⅲ clopidogrel resistance Ⅲ antiplatelet agents Ⅲ cardiovascular diseases Ⅲ cerebrovascular diseases A spirin and the thienopyridines ticlopidine and clopidogrel are inhibitors of platelet aggregation that display good antithrombotic activity. They are used in the prophylaxis of patients undergoing vascular grafting or percutaneous angioplasty, in the medical management of acute coronary syndromes, and in long-term prevention of cardiovascular and cerebrovascular events.Both aspirin and the thienopyridines selectively inhibit a single pathway of platelet activation: aspirin affects the arachidonate-thromboxane A 2 (TxA 2 ) pathway by irreversibly inhibiting cyclo-oxygenase-1 (COX-1) (Figure 1). 1 The thienopyridines affect the adenosine diphosphate (ADP) pathway, by irreversibly blocking the ADP receptor P2Y 12 ( Figure 1). 2 Despite their selective mechanism of action, which does not counteract the many alternative pathways for platelet activation, aspirin and thienopyridines display a good antithrombotic activity. This is explained by the fact that both the arachidonate-TxA 2 pathway and the ADP pathway contribute to the amplification of platelet activation and are essential for the full aggregation and secretion response of platelets to agonists. 2

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Section: True Aspirin Resistancementioning

confidence: 99%

Section: True Aspirin Resistancementioning

confidence: 99%

Aspirin and Clopidogrel

Cattaneo

2004

ATVB

371

133

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“…Some study the prevalence of aspirin resistance and how to achieve defining its presence, [6][7][8] some study the mechanisms for aspirin resistance, [9][10][11][12] and yet others examine the impact or clin-ical significance of aspirin resistance on the presence or development of cardiovascular disease [13][14][15][16][17][18][19][20][21] (Table I). There is no consensus on the ideal technique for the assessment of the presence of aspirin resistance and therefore no agreement about a standardized definition.…”

Section: Discussionmentioning

confidence: 99%

Aspirin resistance, an emerging, often overlooked, factor in the management of patients with coronary artery disease

Makaryus

2006

Clinical Cardiology

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Summary:Aspirin is the most widely used medication in patients with cardiovascular disease. It has had a greater effect on patients with cardiovascular disease than any other drug. With the importance of aspirin now known for decades, it is recently becoming clearer that some patients do not derive as great a benefit from this "wonder drug" secondary to their resistance to its effects. Aspirin resistance, its prevalence, its identification, and how to overcome or avert it with other medications then becomes a central topic of discussion as important, if not more so, than the importance of aspirin itself as a cornerstone in the treatment of patients with cardiovascular disease. This review explores the current understanding of the mechanism of aspirin resistance with regard to its prevalence and the magnitude of its clinical significance. It also examines the therapeutic implications of a diagnosis of aspirin resistance.

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“…(Pignone, Alberts et al 2010) 3.3 Aspirin resistance Aspirin resistance, defined as failure of suppression of thromboxane generation, increases the risk of cardiovascular events in a high-risk population. (Eikelboom, Hirsh et al 2002) Causes of aspirin resistance include concurrent use of nonsteroidal anti-inflammatory drugs such as ibuprofen that may compete with aspirin at the COX-1 receptor site, (CatellaLawson, Reilly et al 2001) polymorphisms in the COX-1 gene, (Eikelboom, Hirsh et al 2002;Halushka and Halushka 2002) poor glucose control, body weight, and conditions associated with a high platelet turnover. (Zimmermann, Wenk et al 2003;Zimmermann, Kurt et al 2005;Guthikonda, Lev et al 2007;Modica, Karlsson et al 2007) …”

Section: Aspirin As a Secondary Prevention Strategy In Diabetes Mellitusmentioning

confidence: 99%

Diabetes and Aspirin Resistance

Yaturu¹

2011

Recent Advances in the Pathogenesis, Prevention and Management of Type 2 Diabetes and Its Complications

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Why Are Some Individuals Resistant to the Cardioprotective Effects of Aspirin?

Cited by 101 publications

References 24 publications

Aspirin and Clopidogrel

Aspirin and Clopidogrel

Aspirin resistance, an emerging, often overlooked, factor in the management of patients with coronary artery disease

Diabetes and Aspirin Resistance

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