Lack of aspirin effect: aspirin resistance or resistance to taking aspirin?

Cotter, Gad; Shemesh, Eyal; Zehavi, Miriam; Dinur, Irit; Rudnick, Abraham; Milo, Olga; Vered, Zvi; Krakover, Ricardo; Kaluski, Edo; Kornberg, Abraham

doi:10.1016/j.ahj.2003.07.011

Cited by 145 publications

(126 citation statements)

References 17 publications

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“…In addition, the biosynthesis of TXA2 via pathways not inhibited by aspirin as well as alternative pathways involved in platelet activation not blocked by aspirin (e.g., those involving adenosine 5'-diphosphate (ADP), collagen, epinephrine, and thrombin) may play a role in AR. Moreover, the majority of AR reported in the literature may be the result of poor adherence [10][11][12] . The genetic etiology of AR has also been proposed.…”

Section: Study Populationsmentioning

confidence: 99%

Platelet Response to Aspirin in Chinese Stroke Patients is Independent of Genetic Polymorphisms of COX-1 C50T and COX-2 G765C

Zhou

Lin

et al. 2013

JAT

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Aim: Aspirin resistance (AR) is common in Chinese stroke patients taking antiplatelet medications; however, few studies have documented the role of cyclooxygenase (COX)-1 C50T and COX-2 G765C polymorphisms in AR. The aim of this study was to investigate the prevalence of AR in Chinese stroke patients and the relationships between AR and COX-1 C50T and COX-2 G765C polymorphisms, and to evaluate the effect of these polymorphisms on platelet response to aspirin. Methods: We prospectively enrolled 634 Chinese stroke patients. Platelet aggregation testing was performed before and after aspirin administration. The pre-and post-aspirin levels of 11-dehydrothromboxane B2 (11-dTxB2) were determined in urine samples. COX-1 C50T and COX-2 G765C genotypes were determined by a polymerase chain reaction-allelic restriction assay. Results: AR was detected in 129 patients (20.4%), aspirin semi-resistance (ASR) was detected in 28 patients (4.4%), and aspirin sensitivity (AS) was detected in 477 patients (75.2%). There was no association between COX-1 C50T or COX-2 G765C polymorphisms and ASR＋AR. Aspirin could efficiently reduce 11-dTxB2 production by approximately 75%. In addition, platelet aggregation, both in response to arachidonic acid (AA) and adenosine 5'-diphosphate (ADP), was inhibited by more than 80% and 40%, respectively; however, the percentage reduction in platelet aggregation and 11-dTxB2 levels was not significantly different between the COX-1 C50T and COX-2 G765C genotypes (p＞0.05). Conclusions: There was no association between COX-1 C50T and COX-2 G765C polymorphisms and AR in Chinese stroke patients. In addition, COX-1 C50T and COX-2 G765C polymorphisms had no effect on the platelet response to aspirin. J Atheroscler Thromb, 2013; 20:65-72.

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Section: Study Populationsmentioning

confidence: 99%

Platelet Response to Aspirin in Chinese Stroke Patients is Independent of Genetic Polymorphisms of COX-1 C50T and COX-2 G765C

Zhou

Lin

et al. 2013

JAT

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“…69 Another mechanism of aspirin resistance that should never be laid aside is lack of compliance, which, in a recent study, accounted for the majority of poor aspirin response and was the only significant mediator of poor clinical outcome. 70 …”

Section: True Aspirin Resistancementioning

confidence: 99%

Aspirin and Clopidogrel

Cattaneo

2004

ATVB

368

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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“…This effect has not been shown with COX-2 selective rofecoxib or diclofenac [31]. Poor compliance, drug interactions especially those reduce enteral absorption of aspirin such as proton pump inhibitors [32][33][34], long-term aspirin treatment (tachyphylaxis) [35] and genetic polymorphisms involving COX-1 and COX-2 have been reported as the reasons for reduced response to aspirin treatment [36,37]. Our results suggest that aspirin non-responsiveness is not so frequent in our population as reported previously by the point of care test PFA-100.…”

Section: Discussionmentioning

confidence: 99%