High on-treatment platelet reactivity in transcatheter aortic valve implantation patients

Polzin, Amin; Schleicher, Mathias; Seidel, H.; Scharf, Rüdiger E.; Merx, Marc W.; Kelm, Malte; Zeus, Tobias

doi:10.1016/j.ejphar.2015.01.028

Cited by 39 publications

(20 citation statements)

References 17 publications

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“…In our investigations, incidence of HTPR to aspirin was between 4 and 62% in different patient cohorts [17][18][19][20][21]. Higher rates of MACCE and a worse clinical outcome have been described in patients with HTPR [21][22][23][24][25].…”

Section: Discussionmentioning

confidence: 99%

Malondialdehyde Assay in the Evaluation of Aspirin Antiplatelet Effects

et al. 2018

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Aspirin is essential in secondary prevention of patients after myocardial infarction and with coronary artery disease. However, impaired pharmacodynamic response to aspirin is frequent (high on-treatment platelet reactivity [HTPR]). This leads to an enhanced prevalence of cardiovascular events and to an impaired clinical outcome. The current specific assays to evaluate aspirin antiplatelet effects are complex, time-consuming and demand for a high laboratory expertise. Therefore, we developed a potentially bedside assay based on the determination of malondialdehyde (MDA). MDA is a by-product of the thromboxane (TX) formation, which is synthesized in equimolar concentrations. In this study, we compared this MDA assay to the conventional assays in determination of pharmacodynamic aspirin response. For this, aspirin antiplatelet effects were measured in 22 healthy individuals and 63 aspirin treated patients using TX B2 formation enzyme-linked antibody assay, arachidonic acid induced light transmission aggregometry (LTA) and the new fluorometric MDA assay. In patients, MDA levels correlated well with TX formation (R = 0.81; 95% CI 0.69–0.88; p < 0.001) and LTA (R = 0.84; CI 0.74–0.91; p < 0.001). Receiver operating characteristic analyses revealed that the MDA assay does detect HTPR to aspirin sufficiently (area under the curve: 0.965; p < 0.001). The optimal cut-off was > 128 nmol/L (sensitivity of 100%, specificity of 91%). The new MDA assay is reliable in detecting HTPR. It is highly specific in the evaluation of antiplatelet effects by aspirin. This promising and potential bedside assay needs to be evaluated in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Malondialdehyde Assay in the Evaluation of Aspirin Antiplatelet Effects

et al. 2018

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“…HTPR to antiplatelet medication is frequent [9,10]. However, the incidence of HTPR to antiplatelet medication has been reported to show a very high range between 3 and 62% [11].…”

Section: Discussionmentioning

confidence: 99%

Thromboxane Formation Assay to Identify High On-Treatment Platelet Reactivity to Aspirin

Mohring

Piayda²,

Dannenberg³

et al. 2017

Pharmacology

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Platelet inhibition by aspirin is indispensable in the secondary prevention of cardiovascular events. Nevertheless, impaired aspirin antiplatelet effects (high on-treatment platelet reactivity [HTPR]) are frequent. This is associated with an enhanced risk of cardiovascular events. The current gold standard to evaluate platelet hyper-reactivity despite aspirin intake is the light-transmittance aggregometry (LTA). However, pharmacologically, the most specific test is the measurement of arachidonic acid (AA)-induced thromboxane (TX) B2 formation. Currently, the optimal cut-off to define HTPR to aspirin by inhibition of TX formation is not known. Therefore, in this pilot study, we aimed to calculate a TX formation cut-off value to detect HTPR defined by the current gold standard LTA. We measured platelet function in 2,507 samples. AA-induced TX formation by ELISA and AA-induced LTA were used to measure aspirin antiplatelet effects. TX formation correlated nonlinearly with the maximum of aggregation in the AA-induced LTA (Spearman's rho R = 0.7396; 95% CI 0.7208-0.7573, p < 0.0001). Receiver operating characteristic analysis and Youden's J statistics revealed 209.8 ng/mL as the optimal cut-off value to detect HTPR to aspirin with the TX ELISA (area under the curve: 0.92, p < 0.0001, sensitivity of 82.7%, specificity of 90.3%). In summary, TX formation ELISA is reliable in detecting HTPR to aspirin. The calculated cut-off level needs to be tested in trials with clinical end points.

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“…Dual antiplatelet therapy (DAPT) is indispensable in patients after acute myocardial infarction and in patients undergoing cardiac interventions. However, it is well known that there is substantial interindividual variability in the pharmacodynamic response to antiplatelet medication . Furthermore, it has been shown that high on‐treatment platelet reactivity (HTPR) is associated with ischemic events, and that low on‐treatment platelet reactivity (LTPR) is associated with bleeding .…”

Section: Introductionmentioning

confidence: 99%

Platelet function testing: dead or alive

Helten

Naguib

Dannenberg

et al. 2018

Journal of Thrombosis and Haemostasis

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Background High on-treatment platelet reactivity (HTPR) to antiplatelet medication leads to ischemic events, whereas low on-treatment platelet reactivity (LTPR) increases bleeding risk. However, various trials have failed to demonstrate superiority of tailored antiplatelet regimens (ARCTIC, ANTARCTIC, Trigger-PCI, and GRAVITAS). TROPICAL-ACS was the first study that demonstrated the benefit of tailoring antiplatelet medication according to platelet function analysis. A potential reason may be that different platelet function assays were used in these trials. Objectives To evaluate whether the results of platelet function tests are comparable. Patients/Methods We tested three commonly used assays - light transmission aggregometry (LTA), (Multiplate impedance aggregometry [MP]), and vasodilator-stimulated phosphoprotein phosphorylation assay (VASP) - in 23 patients receiving dual antiplatelet therapy with aspirin and clopidogrel. Results With LTA, HTPR occurred in 57% of patients; with VASP, it occurred in 43% of patients; and with MP, it occurred in 13% of patients. According to LTA, only 35% of patients were in the therapeutic window; according to VASP, 57% of patients were in the therapeutic window; and according to MP, 48% of patients were in the therapeutic window. With LTA, LTPR occurred in 9% of patients; with VASP, it occurred in 0% of patients; and with MP, it occurred in 39% of patients. Therefore, the prevalences of HTPR and LTPR differed significantly between assays. Remarkably, in 17% of patients, one assay showed HTPR whereas another showed LTPR. Conclusions The results of different platelet function assays differ substantially. Up to now, only TROPICAL-ACS had demonstrated a benefit of tailoring antiplatelet medication according to platelet function analysis. Future trials are needed to evaluate whether the platelet function assay used in TROPICAL-ACS is the 'correct' one and revives platelet function testing.

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High on-treatment platelet reactivity in transcatheter aortic valve implantation patients

Cited by 39 publications

References 17 publications

Malondialdehyde Assay in the Evaluation of Aspirin Antiplatelet Effects

Malondialdehyde Assay in the Evaluation of Aspirin Antiplatelet Effects

Thromboxane Formation Assay to Identify High On-Treatment Platelet Reactivity to Aspirin

Platelet function testing: dead or alive

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