Cardiovascular Death and Nonfatal Myocardial Infarction in Acute Coronary Syndrome Patients Receiving Coronary Stenting Are Predicted by Residual Platelet Reactivity to ADP Detected by a Point-of-Care Assay

Marcucci, Rossella; Gori, Anna Maria; Paniccia, Rita; Giusti, Betti; Valente, Serafina; Giglioli, Cristina; Buonamici, Piergiovanni; Antoniucci, David; Abbate, Rosanna; Gensini, Gian Franco

doi:10.1161/circulationaha.108.812636

Cited by 499 publications

(345 citation statements)

References 24 publications

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“…patients with stable coronary artery disease (CAD) or unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI)], but the issue of HTPR of patients needing emergent intervention [i.e. patients with ST-segment elevation myocardial infarction (STEMI)] or patients receiving glycoprotein-blockers has been less intensively investigated (14)(15)(16)(17), although this is a common situation in a "real-life" setting. There is so far no consecutive registry that evaluates the clinical outcome in unselected patients that have been admitted for PCI and coronary stenting with regard to different platelet function tests.…”

Section: Introductionmentioning

confidence: 99%

Multiple electrode aggregometry and vasodilator stimulated phosphoprotein-phosphorylation assay in clinical routine for prediction of postprocedural major adverse cardiovascular events

Freynhofer¹,

Brozovic²,

Bruno³

et al. 2011

Thromb Haemost

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SummaryReduced antiplatelet effect of clopidogrel assessed with multiple electrode aggregometry (MEA) and vasodilator stimulated phosphoprotein-phosphorylation (VASP-P) assay has been proven to predict major adverse cardiovascular events (MACE) after coronary stenting. So far no consecutive registry has evaluated the usefulness of different adenosine diphosphate-based platelet function tests to predict outcome in unselected patients. Hence, our objective was to determine the feasibility of MEA and VASP-P for clinical routine and whether low-response to clopidogrel as determined by MEA and/or the VASP-P assays predicts MACE in a "real-life" population undergoing coronary stenting. Threehundred consecutive patients were included in this prospective registry. Blood was sampled 6-24 hours after stenting to measure MEA and VASP-P. The use of glycoprotein-IIb/IIIa-blockers limited MEA to 196 measurements. Concerning the VASP-P assay, 300 measurements were achieved. Receiver Operating Characteristics (ROC)-curves of sensitiv- ity and specificity estimates for MACE were plotted for VASP-P assay. The area under the ROC-curve was 0.683 (p=0.014) for the platelet reactivity index (PRI) calculated from median fluorescence intensities (FI) with an optimal cut-off at 60.2% PRI. Patients above 60.2% had a significantly increased risk for MACE at six months follow-up (p=0.007). Estimating the cut-offs for the PRI from mean FI (52%) or from geometric mean FI (56.6%) led to clinically relevant differences. VASP-P assay is feasible for clinical routine to measure clopidogrel effects and to predict post-procedural MACE in unselected patients. With regard to differing cut-offs, exact standardisation of the VASP-P assay is mandatory. The use of GP-IIb/IIIa-blockers prevents MEA testing and limits its usability in unselected patients.

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Section: Introductionmentioning

confidence: 99%

Multiple electrode aggregometry and vasodilator stimulated phosphoprotein-phosphorylation assay in clinical routine for prediction of postprocedural major adverse cardiovascular events

Freynhofer¹,

Brozovic²,

Bruno³

et al. 2011

Thromb Haemost

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“…Multiple studies indicate high residual platelet reactivity, also referred to as clopidogrel "resistance" or "non-responsiveness", is associated with poor clinical outcomes (1)(2)(3)(4)(5). However, we (6) and others (2) have suggested that a portion of platelet function following treatment with standard dose clopidogrel (300 mg loading dose [LD], 75 mg daily maintenance dose [MD]) is accounted for by pretreatment platelet reactivity -and that clopidogrel "resistance" or "non-responsiveness" may therefore not be appropriate terms.…”

Section: Introductionmentioning

confidence: 99%

Intrinsic platelet reactivity before P2Y12 blockade contributes to residual platelet reactivity despite high-level P2Y12 blockade by prasugrel or high-dose clopidogrel

Frelinger¹,

Michelson²,

Wiviott³

et al. 2011

Thromb Haemost

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SummaryIt was the objective of this study to determine whether the intrinsic platelet response to adenosine diphosphate (ADP) before thienopyridine exposure contributes to residual platelet reactivity to ADP despite high level P2Y 12 blockade by prasugrel (60 mg loading dose [LD]), 10 mg daily maintenance dose [MD]) or high-dose clopidogrel (600 mg LD, 150 mg daily MD). High residual platelet function during clopidogrel therapy is associated with poor clinical outcomes. It remains unknown whether the relationship between platelet reactivity prior to treatment with clopidogrel (300 mg LD, 75 mg daily MD) and residual on-treatment platelet reactivity is maintained after more potent P2Y 12 inhibition. PRINCIPLE-TIMI 44 was a randomised, double-blind, twophase crossover study of prasugrel compared with high-dose clopidogrel in 201 patients undergoing cardiac catheterisation for planned percutaneous coronary intervention. ADP-stimulated platelet-monocyte aggregates, platelet surface P-selectin and platelet aggregation were measured pre-treatment, during LD (6 h and 18-24 h) and MD (15 d). Correlations of pre-treatment to on-treatment values were determined by Spearman rank order. Prasugrel resulted in greater platelet inhibition than high-dose clopidogrel for each measure. However, for both drugs, pre-treatment reactivity to ADP predicted 6 h, 18-24 h and 15 day reactivity to ADP (correlations 0.24-0.62 for platelet-monocyte aggregates and P-selectin). In conclusion, a patient's intrinsic platelet response to ADP before exposure to thienopyridines contributes to residual platelet reactivity to ADP despite high level P2Y 12 blockade with high-dose clopidogrel or even higher level P2Y 12 blockade with prasugrel. Patients who are hyper-responsive to ADP pre-treatment are more likely to be hyper-responsive to ADP on-treatment, which may be relevant to therapeutic strategies.

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“…В литературе накапливается все больше доказательств того, что высокие значения остаточной реактивности тромбоцитов, определенные in vitro у пациентов, получающих ДАТ, сопровождается риском таких нежелательных явлений, как тромбоз стента и смерть от сердечно-сосудистых событий [12,13]. В исследовании RECLOSE [14] у лиц с лабора-торной резистентностью к проводимой ДАТ частота тромбоза стента оказалась значительно выше, чем у больных, чувствительных к АТ.…”

Section: Discussionunclassified

The “Protocol” Study: Preliminary Results

et al. 2015

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Aim.To reveal the association of gene polymorphism CYP2С19*2 and recurrent early stent thrombosis in coronary vessels, and paradoxal response to clopidogrel intake in patients -the inhabitants of Siberian Region -after acute coronary syndrome. Material and methods. Totally 105 patients studied, hospitalized for stenting of coronary arteries in acute coronary syndrome, never received clopidogrel previously. The polymorphism of studied СУР2С19: *2, *3, *17 alleles, as assessment of platelet aggregation with ADP before and after clopidogrel intake, as of endpoints on safety and efficacy during 30 days (thrombotic complications, bleeding). Results. Within the selected patients there was no any significant association of any CYP2С19*2 and/or CYP2С19*3 alleles and paradoxic laboratory reaction. There was significant association of the CYP2C19*17 gene carriage and bleedings. When comparing the groups of patients having or not having complications related to clopidogrel (thrombotic or bleedings), there was significant difference in residual platelet aggregation. Conclusion.The results of the study might be strongly significant for the decisions making on double antiplatelet therapy and on the tactics of drugs preference. Russ

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Cardiovascular Death and Nonfatal Myocardial Infarction in Acute Coronary Syndrome Patients Receiving Coronary Stenting Are Predicted by Residual Platelet Reactivity to ADP Detected by a Point-of-Care Assay

Cited by 499 publications

References 24 publications

Multiple electrode aggregometry and vasodilator stimulated phosphoprotein-phosphorylation assay in clinical routine for prediction of postprocedural major adverse cardiovascular events

Multiple electrode aggregometry and vasodilator stimulated phosphoprotein-phosphorylation assay in clinical routine for prediction of postprocedural major adverse cardiovascular events

Intrinsic platelet reactivity before P2Y12 blockade contributes to residual platelet reactivity despite high-level P2Y12 blockade by prasugrel or high-dose clopidogrel

The “Protocol” Study: Preliminary Results

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