Aspirin non-responsiveness as measured by PFA-100 in patients with coronary artery disease

Andersen, Kjell; Hurlen, Mette; Arnesen, Harald; Seljeflot, Ingebjørg

doi:10.1016/s0049-3848(02)00405-x

Cited by 200 publications

(158 citation statements)

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“…Eight studies were eliminated because they were not prospective studies, 4 because they reported only clopidogrel resistance, 2 because they did not evaluate clinical cardiovascular recurrences during the follow-up but only surrogate markers, and 1 because only a meeting abstract was available. As a result, a total of 11 prospective studies were included in the meta-analysis [8][9][10][11][12][13][14][15][16][17][18].…”

Section: Search Resultsmentioning

confidence: 99%

Residual platelet reactivity on aspirin therapy and recurrent cardiovascular events — A meta-analysis

Sofi

Marcucci

Gori

et al. 2008

International Journal of Cardiology

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Background: Recently, a growing body of evidence on the possible role of residual platelet reactivity (RPR) in affecting clinical events has accumulated. The aim of this study was to systematically assess the relationship between RPR on acetylic salicylic acid (ASA) therapy and the occurrence of recurrent events in a meta-analysis of prospective studies. Methods: A systematic literature search of MEDLINE, EMBASE, Science Citation Index, the Cochrane Systematic Review Database and bibliographies of retrieved articles through May 2007 was conducted. Studies were included if they analysed RPR in coronary heart disease patients in relation to the occurrence of adverse coronary events during follow-up. Results: Eleven prospective studies, incorporating 1952 patients with coronary heart disease followed for a time ranging from 6 days to 4 years, met the inclusion criteria. The pooled analysis demonstrated a significantly increased relative risk of adverse clinical events during follow-up for patients with RPR on ASA therapy (RR: 3.11, 95%CI 1.88-5.15; p b 0.0001). Moreover, the association between RPR and cardiovascular recurrences remained to be statistically significant even when subgroup analyses performed according to the duration of follow-up, ASA dosage, characteristics of the study population, and laboratory method were conducted. Conclusions: The present meta-analysis documents a significant association between RPR on ASA treatment and recurrent cardiovascular events. More prospective studies are needed to determine the independent prognostic importance of RPR during aspirin therapy and possible benefit of individually tailored anti-platelet treatment strategies in these patients.

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Section: Search Resultsmentioning

confidence: 99%

Residual platelet reactivity on aspirin therapy and recurrent cardiovascular events — A meta-analysis

Sofi

Marcucci

Gori

et al. 2008

International Journal of Cardiology

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“…As a matter of fact, Chakroun et al recently showed that high plasma VWF levels are the main determinant of short PFA-100 closure time in patients with cardiovascular disease on aspirin treatment, 61 and Watala et al demonstrated that VWF interaction with GPIb and GPIIb/IIIa is the major determinant of PFA-100 closure time, whereas other platelet receptors and mechanisms leading to platelet aggregation are of minor significance. 63 These findings explain the relatively high prevalence of short PFA-100 closure time in patients on aspirin treatment for cardiovascular or cerebrovascular disease, 42,43,[57][58][59][60][61][62] because these patients tend to have higher than normal levels of plasma VWF. Therefore, because aspirin does not inhibit the major determinants of the PFA-100 closure time, it appears that the PFA-100 system is not an adequate method to measure platelet inhibition by aspirin.…”

Section: Failure Of Aspirin To Inhibit Platelet Function In Vivo or Imentioning

confidence: 99%

“…This could easily account for the high percentage of subjects with short closure time despite being on aspirin treatment. 42,43,[57][58][59][60][61][62] Because the PFA-100 system studies platelet function under flow conditions that are characterized by high shear, plasma VWF is a major determinant of closure time. As a matter of fact, Chakroun et al recently showed that high plasma VWF levels are the main determinant of short PFA-100 closure time in patients with cardiovascular disease on aspirin treatment, 61 and Watala et al demonstrated that VWF interaction with GPIb and GPIIb/IIIa is the major determinant of PFA-100 closure time, whereas other platelet receptors and mechanisms leading to platelet aggregation are of minor significance.…”

Section: Failure Of Aspirin To Inhibit Platelet Function In Vivo or Imentioning

confidence: 99%

“…A clear demonstration of this comes from the study of Andersen et al, who showed that aspirin treatment abolished TxB 2 production to the same extent in patients with short closure time ("aspirin resistant") and patients with long closure time ("aspirin sensitive"). 57 The Ultegra Rapid Platelet Function Assay-ASA measures the agglutination of fibrinogen-coated beads by platelets stimulated by an agonist in citrated whole blood. Although the specificity of the test for aspirin inhibition is reported to be 85% by the manufacturer, 64,65 it is also sensitive to GPIIb/IIIa inhibitors, dipyridamole, clopidogrel, and streptokinase, 65 suggesting that it is far from the ideal specific test for measuring the effect of aspirin on platelets.…”

Section: Failure Of Aspirin To Inhibit Platelet Function In Vivo or Imentioning

confidence: 99%

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Aspirin and Clopidogrel

Cattaneo

2004

ATVB

370

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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“…Thus, the term ''aspirin treatment failure'' has been used to describe the occurrence of any atherothromboembolic ischemic events in compliant patients [8,9]. On the other hand, the term ''aspirin resistance'' detected with laboratory tests is used to define the failure of aspirin to inhibit the thromboxane A2 production or the platelet aggregation and varies from 0.5% to 45% [10][11][12]. The direct correlation between the laboratory and the clinical aspirin resistance has been shown previously [13,14], however, a clinical tool that predict ASA resistance is still lacking.…”

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confidence: 99%