Key result
In vitro serotonin receptor antagonism with ketanserin significantly decreased ADP-induced platelet aggregation in clopidogrel low-responders from 59.9% to 37.4% (p<0.01).
Why the study?
Does in vitro serotonin antagonism reduce high on-treatment platelet reactivity in clopidogrel low-responders after coronary stent placement?
Does in vitro serotonin antagonism reduce high on-treatment platelet reactivity in clopidogrel low-responders after coronary stent placement?
Absolute Event Rate: 37.4% vs 59.9%
p-value: p=<0.01
In vitro serotonin receptor antagonism with ketanserin significantly improves platelet inhibition in CAD patients who are low-responders to clopidogrel after coronary stenting.
May support trials of serotonin antagonism to overcome clopidogrel resistance; leaves open clinical efficacy after stenting.
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.
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Duerschmied et al. (2012) studied Coronary artery disease after coronary stent placement (n=61). Ketanserin (serotonin receptor antagonist) vs. Vehicle (no ketanserin) was evaluated on ADP-induced platelet aggregation in clopidogrel low-responders (p=<0.01). In vitro serotonin receptor antagonism with ketanserin significantly decreased ADP-induced platelet aggregation in clopidogrel low-responders from 59.9% to 37.4% (p<0.01).
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