Beschreibung:
<jats:title>Abstract</jats:title>
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<jats:title>Background</jats:title>
<jats:p>Poor platelet inhibition by aspirin or clopidogrel has been associated with adverse outcomes in patients with cardiovascular diseases. A reliable and facile assay to measure platelet inhibition after treatment with aspirin and a P2Y<jats:sub>12</jats:sub> antagonist is lacking. Multiple electrode aggregometry (MEA), which is being increasingly used in clinical studies, is sensitive to platelet inhibition by aspirin and clopidogrel, but a critical evaluation of MEA monitoring of dual anti-platelet therapy with aspirin and P2Y<jats:sub>12</jats:sub> antagonists is missing.</jats:p>
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<jats:title>Design and Methods</jats:title>
<jats:p>By performing <jats:italic>in vitro</jats:italic> and <jats:italic>ex vivo</jats:italic> experiments, we evaluated in healthy subjects the feasibility of using MEA to monitor platelet inhibition of P2Y<jats:sub>12</jats:sub> antagonists (clopidogrel <jats:italic>in vivo</jats:italic>, cangrelor <jats:italic>in vitro</jats:italic>) and aspirin (100 mg per day <jats:italic>in vivo</jats:italic>, and 1 mM or 5.4 mM <jats:italic>in vitro</jats:italic>) alone, and in combination. Statistical analyses were performed by the Mann-Whitney rank sum test, student' t-test, analysis of variance followed by the Holm-Sidak test, where appropriate.</jats:p>
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<jats:title>Results</jats:title>
<jats:p>ADP-induced platelet aggregation in hirudin-anticoagulated blood was inhibited by 99.3 ± 1.4% by <jats:italic>in vitro</jats:italic> addition of cangrelor (100 nM; p < 0.001) and by 64 ± 35% by oral clopidogrel (600 mg) intake (p < 0.05; values are means ± SD). Pre-incubation of blood with aspirin (1 mM) or oral aspirin intake (100 mg/day for 1 week) inhibited arachidonic acid (AA)-stimulated aggregation >95% and 100 ± 3.2%, respectively (p < 0.01). Aspirin did not influence ADP-induced platelet aggregation, either <jats:italic>in vitro</jats:italic> or <jats:italic>ex vivo</jats:italic>. Oral intake of clopidogrel did not significantly reduce AA-induced aggregation, but P2Y<jats:sub>12</jats:sub> blockade by cangrelor (100 nM) <jats:italic>in vitro</jats:italic> diminished AA-stimulated aggregation by 53 ± 26% (p < 0.01). A feasibility study in healthy volunteers showed that dual anti-platelet drug intake (aspirin and clopidogrel) could be selectively monitored by MEA.</jats:p>
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<jats:title>Conclusions</jats:title>
<jats:p>Selective platelet inhibition by aspirin and P2Y<jats:sub>12</jats:sub> antagonists alone and in combination can be rapidly measured by MEA. We suggest that dual anti-platelet therapy with these two types of anti-platelet drugs can be optimized individually by measuring platelet responsiveness to ADP and AA with MEA before and after drug intake.</jats:p>
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