Abstract
Increased residual platelet reactivity remains a burden for coronary artery disease (CAD) patients who received a coronary stent and do not respond sufficiently to treatment with acetylsalicylic acid and clopidogrel. We hypothesized that serotonin antagonism reduces high on-treatment platelet reactivity. Whole blood impedance aggregometry was performed with arachidonic acid (AA, 0.5 mM) and adenosine diphosphate (ADP, 6.5 µM) in addition to different concentrations of serotonin (1–100 µM) in whole blood from 42 CAD patients after coronary stent placement and 10 healthy subjects. Serotonin increased aggregation dose-dependently in CAD patients who responded to clopidogrel treatment: After activation with ADP, aggregation increased from 33.7±1.3% to 40.9±2.0% in the presence of 50 µM serotonin (p<0.05) and to 48.2±2.0% with 100 µM serotonin (p<0.001). The platelet serotonin receptor antagonist ketanserin decreased ADP-induced aggregation significantly in clopidogrel low-responders (from 59.9±3.1% to 37.4±3.5, p<0.01), but not in clopidogrel responders. These results were confirmed with light transmission aggregometry in platelet-rich plasma in a subset of patients. Serotonin hence increased residual platelet reactivity in patients who respond to clopidogrel after coronary stent placement. In clopidogrel low-responders, serotonin receptor antagonism improved platelet inhibition, almost reaching responder levels. This may justify further investigation of triple antiplatelet therapy with anti-serotonergic agents.
Highlights
In myocardial infarction - the critical event in coronary artery disease (CAD) - plaque rupture initiates platelet activation resulting in atherothrombotic coronary artery occlusion [1]
CAD patients gave verbal informed consent for additional ex vivo measurements with routinely acquired platelet aggregometry blood samples and written consent was acquired retrospectively to comply with ethical guidelines
Study subjects The 42 included CAD patients who were treated with ASA and clopidogrel showed a typical risk profile and 57% presented with acute coronary syndrome
Summary
In myocardial infarction - the critical event in coronary artery disease (CAD) - plaque rupture initiates platelet activation resulting in atherothrombotic coronary artery occlusion [1]. Percutaneous coronary intervention with stent placement is the standard of care treatment for patients with critical CAD [2,3]. In acute coronary syndrome the newer P2Y12 receptor antagonists ticagrelor and prasugrel are preferred, but clopidogrel remains the standard substance when ticagrelor or prasugrel are contraindicated or unavailable and in patients undergoing elective stenting. High on-treatment platelet reactivity to ADP is associated with adverse clinical event occurrence, but the wide variety of definitions of residual platelet reactivity has only recently been addressed by a consensus statement [12]. To date, it is not clear which measure of platelet reactivity and which cut-off points should be used
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