Higher P-selectin expression in ACS patients treated with clopidogrel is associated with subsequent atherothrombotic events; much lower P-selectin expression is seen in patients treated with prasugrel. Sue Fox, Mark Thomas, Yanushi Wijeyeratne, Jane May,
Andrew Johnson, Stan Heptinstall. Cardiovascular Medicine, University of Nottingham, UK
Introduction
There is wide variation in platelet response to
P-selectin test
clopidogrel and evidence is emerging that high on-
treatment platelet reactivity is associated with
further atherothrombotic events. We have
developed a simple, remotely performed blood test
based on measurement of platelet P-selectin
expression1 and set out to check whether the results
of this test has prognostic implications. We also
measured platelet P-selectin expression in patients
undergoing treatment with the newer, more potent
12 antagonist, prasugrel. Remotely performed
platelet P-selectin measurements have not been
used before to monitor platelet function in patients
We performed a prospective, observational study in
patients (n=100) taking aspirin (75mg) and
clopidogrel (300mg loading dose and at least one 75mg maintenance dose) after admission to hospital
In a second study, ACS patients (n=18) on aspirin
and prasugrel (60mg loading dose and 10mg
Figure 1 P-selectin test results for ACS patients treated with
maintenance dose) have been compared with a
group of ACS patients treated with clopidogrel
At 9 months follow-up, major adverse events had occurred in
11 patients (6 cardiovascular deaths and 5 myocardial
(1) Fox SC, et al. Platelets 2009; 20(4):250-259
ROC curve analysis determined that the test had a moderate
ability to predict the primary endpoint (area under curve=0.69,
p=0.046). These major adverse events occurred more
frequently in patients with high on-treatment platelet reactivity
Whole blood samples were stimulated with a
compared to those without high on-treatment platelet reactivity
for 5 minutes and fixed (using a fixative agent,
patent applied for). Platelet P-selectin expression
to the blood samples demonstrated that further inhibition is
was measured within 6 days by flow cytometry.
P-selectin test
P-selectin test values obtained for the patients in
the first study were divided into 2 cohorts based on
ROC curve analysis as patients with high on-
treatment platelet reactivity (n=42) or patients
without high on-treatment platelet reactivity
(n=58). The primary endpoint was defined as the
composite of cardiovascular death, myocardial
infarction and stent thrombosis (major adverse
Conclusions clopidogrel prasugrel
Platelet P-selectin measurements obtained using
ogrel prasugrel
the procedure described here demonstrate high
treatment treatment
residual platelet reactivity during clopidogrel
Figure 2 P-selectin test results for ACS patients treated with
therapy in some patients which is related to risk of
aspirin and clopidogrel (n=58) or aspirin and prasugrel (n=18)
subsequent atherothrombotic events. The P-selectin
test demonstrated lower on-treatment platelet
ACS patients on prasugrel treatment had better platelet
reactivity in patients treated with the more potent
inhibition than ACS patients undergoing treatment with
clopidogrel (p<0.0001). Patient follow up data is awaited.
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Higher P-selectin expression in ACS patients treated with