Variability in Platelet Aggregation Following Sustained Aspirin and Clopidogrel Treatment in Patients With Coronary Heart Disease and Influence of the 807 C/T Polymorphism of the Glycoprotein Ia Gene

Angiolillo, Dominick J.; Fernández‐Ortíz, Antonio; Bernardo, Esther; Ramı́rez, Carlos A.; Cavallari, Ugo; Trabetti, Elisabetta; Sabaté, Manel; Jiménez‐Quevedo, Pilar; Hernández, Rosana; Moreno, Raúl; Escaned, Javier; Alfonso, Fernándo; Bañuelos, Camino; Costa, Marco A.; Bass, Theodore A.; Pignatti, Pier Franco; Macaya, Carlos

doi:10.1016/j.amjcard.2005.06.039

Cited by 54 publications

(43 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…13,14 Despite the short-term improvement in platelet response with high loading dosage regimens of clopidogrel, patients may continue to have elevated platelet reactivity in the maintenance phase of antiplatelet therapy. [15][16][17][18][19] Of note, readministration of a loading dose of clopidogrel in patients already on maintenance treatment evokes further platelet inhibition. 20 This observation has raised the hypothesis that an increase of the maintenance dose of clopidogrel may further enhance platelet inhibition, particularly in high-risk patients.…”

Section: Clinical Perspective P 716mentioning

confidence: 99%

“…[15][16][17][18][19] In brief, blood was collected in sodium-citrated tubes. Platelet aggregation was assessed with platelet-rich plasma (PRP) by the turbidimetric method in a 2-channel aggregometer (Chrono-Log 490 Model, Chrono-Log Corp, Havertown, Pa) after stimulus with 5 or 20 mol/L adenosine diphosphate (ADP).…”

Section: Angiolillo Et Al High Clopidogrel Dosing In Diabetes Mellitusmentioning

confidence: 99%

See 1 more Smart Citation

Randomized Comparison of a High Clopidogrel Maintenance Dose in Patients With Diabetes Mellitus and Coronary Artery Disease

et al. 2007

Self Cite

View full text Add to dashboard Cite

Background-After treatment with clopidogrel, patients with type 2 diabetes mellitus (T2DM) have reduced platelet inhibition compared with patients who are not diabetic. Whether platelet inhibition can be enhanced by increasing clopidogrel maintenance dosage in T2DM patients is unknown. The aim of this pilot study was to assess the functional impact of a high maintenance dose in T2DM patients with suboptimal clopidogrel-induced antiplatelet effects. Methods and Results-T2DM patients on chronic dual antiplatelet therapy were screened to identify suboptimal clopidogrel responders. The latter were randomized to 30-day treatment with a standard (75 mg; nϭ20) or high (150 mg; nϭ20) daily maintenance dose. Platelet function was assessed at 3 time points: baseline, 30 days after randomization, and 30 days after resuming standard dosing. Platelet function parameters included adenosine diphosphate-induced (20 and 5 mol/L) maximal and late platelet aggregation, inhibition of platelet aggregation, platelet disaggregation, and P2Y 12 reactivity index. A total of 64 T2DM patients were screened to identify 40 suboptimal responders. After randomization, maximal adenosine diphosphate-induced (20 mol/L) platelet aggregation was significantly reduced in the 150-mg group compared with the 75-mg group (Pϭ0.002; primary end point). However, suboptimal clopidogrel response was still present in 60% of patients on the 150-mg regimen. All other platelet function parameters showed enhanced clopidogrel-induced antiplatelet effects with 150 mg, which returned to baseline values after resumption of standard dosing. Conclusions-A 150-mg maintenance dose of clopidogrel is associated with enhanced antiplatelet effects compared with 75 mg in high-risk T2DM patients. However, enhanced ex vivo platelet reactivity continues to persist, the clinical implications of which are unknown and need to be evaluated in large-scale clinical trials. (Circulation. 2007;115:708-716.)

show abstract

Section: Clinical Perspective P 716mentioning

confidence: 99%

Section: Angiolillo Et Al High Clopidogrel Dosing In Diabetes Mellitusmentioning

confidence: 99%

Randomized Comparison of a High Clopidogrel Maintenance Dose in Patients With Diabetes Mellitus and Coronary Artery Disease

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…The gene encoding α2 integrin has at least 8 polymorphisms, including two silent polymorphisms located within the I domain [5], Phe (TTT/TTC) due to a T/ Moreover, some recent studies had shown relationship between this polymorphism and the prevalence of myocardial infarction [11], stroke [12,13], as well as diabetic retinopathy [14]. There are also studies that have shown influence of this polymorphism on aspirin and clopidogrel efficacy [15]. The 807T allele has been shown to be a risk factor for myocardial infarction, stroke and diabetic retinopathy, probable because of higher density of alpha2 integrin molecules on platelet surface.…”

Section: Introductionmentioning

confidence: 99%

<i>Bgl II</i> Polymorhism of the α2β1 Integrin Gene in Macedonian Population

Pavkovic¹,

Petlichkovski²,

Stojanović³

et al. 2010

Macedonian Journal of Medical Sciences

View full text Add to dashboard Cite

Background. Glycoprotein (GP) Ia/IIa or α2β1 integrin is a platelet receptor for collagen and it mediates platelet adhesion to vascular subendothelium and is involved in thromb formation. Genetic polymorphism of α2β1 known as Bgl II affects the density of platelet GP Ia/IIa receptor on the platelet surface. Recent studies had shown relationship between this polymorphism and the risk of myocardial infarction, stroke, as well as diabetic retinopathy.

show abstract

“…Moreover, platelet reactivity to collagen after 2 years significantly correlated with platelet reactivity to collagen at enrollment, indicating that platelet hypo-or hyperreactivity to collagen is a consistent phenotype within individuals over time, raising the possibility of a genetic component, for example the 807 C/T polymorphism of the glycoprotein Ia gene. 11 This consistent response raises the possibility that platelet hyperreactivity to collagen in these subjects may have pre-dated treatment with aspirin. Indeed, we demonstrated, using a variety of aspirin-sensitive platelet function tests, that a significant proportion of high post-aspirin platelet reactivity could be accounted for by preexisting (prior to exposure to aspirin) platelet reactivity.…”

Section: Article P 1227mentioning

confidence: 99%

Platelet Reactivity With Prolonged Aspirin Treatment

Frelinger

2010

Circ J

View full text Add to dashboard Cite

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp latelets play a critical role in ischemic heart disease, the cause of 10% of all deaths in Japan. 1 Aspirin is the most commonly used antiplatelet agent for secondary prevention of ischemic heart disease, providing an estimated 20-25% reduction in the risk for serious vascular events in high-risk patients. 2,3 Recurrent thrombotic events, however, have been reported in 10-20% of aspirin-treated patients 3 and several studies have found an association between less-than-expected inhibition of in vitro aspirin-sensitive platelet function tests and the occurrence of adverse clinical outcomes. 4-7 Adding complexity to the problem, conflicting results have been obtained with respect to whether aspirin's antiplatelet effect is maintained 8 or attenuated 9 over time. Therefore, the extent to which platelets in Japanese patients are inhibited by aspirin, and the consistency of this inhibition over time, are of great interest. Article p 1227In this issue of the Journal, Ikeda et al have reported on the antiplatelet effect of aspirin and its 2-year change in high cardiovascular risk Japanese patients. 10 Important strengths of that study include the relatively large group of subjects studied (239 at enrollment) over this time interval and that the study addressed the issue of platelet reactivity under reallife conditions in a Japanese population. As was the case with the aspirin-sensitive tests that were found to be associated with poor clinical outcomes, 4-7 the aspirin-sensitive tests evaluated by Ikeda et al, that is, collagen-stimulated light transmission aggregometry and whole blood aggregation measured by screen filtration pressure, measure endpoints many steps removed from aspirin inhibition of platelet cyclooxygenase-1 (COX-1) and must be interpreted in that context. 10 For example, the authors reported that at baseline 27% of aspirin-treated patients produced a threshold platelet aggregation response to 1 mg/L collagen, while only 10% of healthy aspirin-treated donors responded to this dose of collagen. Such patients with high on-treatment platelet reactivity may be at increased risk for poor clinical outcomes. But because many factors other than aspirin inhibition of platelet COX-1 contribute to collagen-stimulated platelet aggregation, not the least of which is the platelet collagen receptor Ia -IIa, 11 it would be more correct to refer to this as platelet hyperreactivity rather than poor response to aspirin. In studies in which platelet COX-1 activity was evaluated by measuring serum thromboxane B2 (TxB2), the most direct measure of platelet COX-1 activity, poor aspirin inhibition of platelet COX-1 was infrequent (<2% of aspirin-treated patients undergoing cardiac catheterization). 12 Nevertheless, high residual serum TxB2 has been associated with adverse clinical outcomes. 13 In the same study, platelet hyperreactivity as measured using a COX-1-independent platelet function assay was also associated with subsequen...

show abstract

Variability in Platelet Aggregation Following Sustained Aspirin and Clopidogrel Treatment in Patients With Coronary Heart Disease and Influence of the 807 C/T Polymorphism of the Glycoprotein Ia Gene

Cited by 54 publications

References 18 publications

Randomized Comparison of a High Clopidogrel Maintenance Dose in Patients With Diabetes Mellitus and Coronary Artery Disease

Randomized Comparison of a High Clopidogrel Maintenance Dose in Patients With Diabetes Mellitus and Coronary Artery Disease

<i>Bgl II</i> Polymorhism of the α2β1 Integrin Gene in Macedonian Population

Platelet Reactivity With Prolonged Aspirin Treatment

Contact Info

Product

Resources

About