Increased platelet aggregation and turnover in the acute phase of ST-elevation myocardial infarction

Funck, Kristian Løkke; Dalsgaard, Jens; Grove, Erik Lerkevang; Hvas, Anne‐Mette; Kristensen, Steen Dalby

doi:10.3109/09537104.2012.738838

Cited by 33 publications

(28 citation statements)

References 44 publications

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“…PRI values at 1, 3 and 6 months). As demonstrated in this study but already previously published, we found a positive association of high PRI at baseline with elevated platelet turnover [30,31]. Future prospective investigations are warranted to show whether the reticulated platelet fraction might represent an important marker for adverse ischemic or bleeding outcome after PCI [32,33].…”

Section: Discussionsupporting

confidence: 58%

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Variability of on-treatment platelet reactivity in patients on clopidogrel

Freynhofer

Bruno²,

Brozovic³

et al. 2013

Platelets

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Response to clopidogrel therapy is subject to inter-individual variability. However, data with regard to on-treatment platelet reactivity over time in patients undergoing coronary stenting are scarce. For this prospective observational study, 102 consecutive patients on dual antiplatelet therapy undergoing coronary stenting due to stable coronary artery disease (CAD; n = 29), non ST-elevation acute coronary syndrome (NSTE-ACS; n = 45) and ST-elevation myocardial infarction (STEMI; n = 28) were enrolled. Vasodilator-stimulated phosphoprotein-phosphorylation assay was performed at baseline, as well as 1, 3 and 6 months thereafter. Platelet reactivity index (PRI) measured after 1, 3 and 6 months was lower compared to baseline values (p < 0.001). Variables responsible for reduced response to clopidogrel at baseline (reticulated platelet fraction, simvastatin therapy) and during steady-state phase (body mass index, blood glucose concentrations, cholesterol/HDL-ratio and quality of life score) were different. High on-treatment platelet reactivity (HTPR)-phenotype (cut-off = 50% PRI) within the first month changed in 31% of stable CAD, 33% of NSTE-ACS and 39% of STEMI patients, respectively. HTPR-phenotype in the steady-state phase (month 1 to 6) changed in 45% of stable CAD, 33% of NSTE-ACS and 25% of STEMI patients. Response to clopidogrel and accordingly platelet function might vary over time, especially when a cut-off based approach, is used. There was a significant reduction of on-treatment platelet reactivity within the first month after percutaneous coronary intervention with stenting which was maintained for up to 6 months. Variables associated with reduced response to clopidogrel at baseline and during steady-state phase were different, as the latter mainly reflected an unfavorable metabolic profile, comprising elevated BMI, blood glucose levels as well as cholesterol/HDL-ratio.

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Section: Discussionsupporting

confidence: 58%

“…In patients with STEMI, there was a significant improvement of P2Y 12 -inhibition over time (baseline compared to 1, 3, and 6 months). Similarly, to patients suffering from NSTE-ACS this improvement can be explained by the fact that patients with STEMI show a diminished response to clopidogrel in the acute phase [28][29][30].…”

Section: Discussionmentioning

confidence: 94%

Variability of on-treatment platelet reactivity in patients on clopidogrel

Freynhofer

Bruno²,

Brozovic³

et al. 2013

Platelets

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show abstract

“…2 These findings are in line with a previous study by our group, showing that platelet turnover is increased in patients with STEMI compared with healthy individuals and patients with stable coronary artery disease. 4 High on-treatment platelet reactivity is a predictor of cardiovascular events in patients with STEMI, undergoing percutaneous coronary intervention, and exploring mechanisms of interindividual differences in the efficacy of antiplatelet drugs is important.…”

Section: To the Editorsupporting

confidence: 93%

Letter by Grove and Kristensen Regarding Article, “Randomized Assessment of Ticagrelor Versus Prasugrel Antiplatelet Effects in Patients With ST-segment–elevation Myocardial Infarction”

Grove

Kristensen

2013

Circ: Cardiovascular Interventions

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We have read with interest the recent article regarding insufficient effect of oral antiplatelet drugs in the acute phase of ST-segmentelevation myocardial infarction (STEMI).1 Alexopoulos et al 1 evaluated platelet inhibition at 0, 1, 2, 6, 24 hours, and 5 days in patients with STEMI, undergoing primary percutaneous coronary intervention. All patients were treated with heparin and aspirin and were randomized to standard loading and maintenance doses of either ticagrelor or prasugrel. The authors reported a high frequency of high on-treatment platelet reactivity at the first 3 time points and concluded that both ticagrelor and prasugrel exhibit an initial delay in the onset of platelet inhibition.These findings concur with our recent study in a similar population of patients with STEMI, undergoing primary percutaneous coronary intervention.2 Our study population was pretreated with clopidogrel, and more than half of the patients had high residual platelet reactivity 4 hours after initiation of antithrombotic treatment. All oral P2Y12-inhibitors thus seem to provide suboptimal platelet inhibition in the acute phase of STEMI. As discussed by Alexopoulos et al, 1 previous studies indicate that antiplatelet drugs have a faster onset of action in healthy individuals and patients with stable coronary artery disease, and delayed platelet inhibition in STEMI may be partly explained by impaired drug absorption.We suggest that an increased platelet turnover in patients with STEMI may reduce the effect of antiplatelet drugs. Thrombopoiesis and the rate of platelet turnover are reflected by the amount of circulating platelets newly released from the bone marrow.3 An accelerated platelet turnover may affect the potency of antiplatelet drugs mainly because an increased number of immature platelets with increased hemostatic potential will circulate in the blood and an increased turnover of the circulating platelet pool counteracts the relatively short half-lives of antiplatelet drugs.In our recent study, both residual platelet aggregation and platelet turnover indices (mean platelet volume, immature platelet fraction, and immature platelet count) were significantly increased in the acute phase of STEMI compared with a stable phase of 3 months after percutaneous coronary intervention.2 These findings are in line with a previous study by our group, showing that platelet turnover is increased in patients with STEMI compared with healthy individuals and patients with stable coronary artery disease. 4High on-treatment platelet reactivity is a predictor of cardiovascular events in patients with STEMI, undergoing percutaneous coronary intervention, and exploring mechanisms of interindividual differences in the efficacy of antiplatelet drugs is important. We propose that an increased platelet turnover may represent such mechanism. DisclosuresDr Grove has received lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim and Pfizer and serves on advisory boards for AstraZeneca and Bristol-Myers Squibb. Increased platelet aggregation a...

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“…It has been evidenced that clopidogrel platelet inhibition varies over time. After PCI, clopidogrel PR decreases from baseline to 1 month [18,19]. Moreover, measurement of PR varies over time in a significant proportion of patients [20].…”

Section: Discussionmentioning

confidence: 96%

Is platelet inhibition correlated with time from last intake on P2Y12 blockers after an acute coronary syndrome? A pilot study

et al. 2016

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Delay from the last intake of drug could be an important and unexplored variable in the biological response to antiplatelet agents after acute coronary syndrome (ACS) discharge. The objective was to define the impact of the delay from P2Y12 blocker intake on the platelet inhibition level. We compared ticagrelor-, prasugrel-, and clopidogrel-treated patients. All consecutive patients, who had been addressed between 2013 and 2014 for ACS, treated with aspirin and a P2Y12 blocker as maintenance dose, were eligible. One month after discharge, blood sample and a questionnaire were proposed to the patient by a nurse blinded to the protocol. On this questionnaire, three questions about name of the drug, regularity of the intakes, and hour of the last intake were collected. The response to antiplatelet therapy was assessed using platelet reactivity index vasodilator-stimulated phosphoprotein (PRI VASP) and % of adenosine-5'-diphosphate-induced aggregation (%ADP).The primary objective of this study was to evaluate the correlation between platelet inhibition and delay from drug intake. We enrolled 474 ACS treated with clopidogrel 75 mg in 182 cases (38% patients), prasugrel in 190 cases (40%), or ticagrelor in 102 patients (22%). We observed a significant correlation between delay from intake and PRI VASP and %ADP for ticagrelor (r = 0.25, p = 0.01; r = 0.21, p = 0.03; respectively). On clopidogrel (r = 0.09, p = 0.24; r = 0.02, p = 0.80; respectively) and prasugrel (r = 0.02, p = 0.82; r = 0.11, p = 0.12 respectively), no correlation exists. In conclusion, ticagrelor, unlike thienopyridines, is associated with a significant correlation between delay from the last intake and platelet inhibition.

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Increased platelet aggregation and turnover in the acute phase of ST-elevation myocardial infarction

Cited by 33 publications

References 44 publications

Variability of on-treatment platelet reactivity in patients on clopidogrel

Variability of on-treatment platelet reactivity in patients on clopidogrel

Letter by Grove and Kristensen Regarding Article, “Randomized Assessment of Ticagrelor Versus Prasugrel Antiplatelet Effects in Patients With ST-segment–elevation Myocardial Infarction”

Is platelet inhibition correlated with time from last intake on P2Y12 blockers after an acute coronary syndrome? A pilot study

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