title: Serotonin antagonism improves platelet inhibition in clopidogrel low-responders after coronary stent placement: an in vitro pilot study.
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.
authors.affiliation: Department of Cardiology and Angiology, University Medical Center Freiburg, Freiburg, Germany. daniel.duerschmied@uniklinik-freiburg.de
authors.forename: Daniel
authors.initials: D
authors.lastname: Duerschmied
authors.forename: Ingo
authors.initials: I
authors.lastname: Ahrens
authors.forename: Maximilian
authors.initials: M
authors.lastname: Mauler
authors.forename: Christoph
authors.initials: C
authors.lastname: Brandt
authors.forename: Stefanie
authors.initials: S
authors.lastname: Weidner
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Martin
authors.initials: M
authors.lastname: Moser
mesh_terms: D000368:Aged; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007650:Ketanserin / Q000737:chemistry; D008027:Light; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism; D010865:Pilot Projects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D012701:Serotonin / Q000737:chemistry*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D012702:Serotonin Antagonists; D012701:Serotonin; D007650:Ketanserin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin