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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.

Source: http://www.plateletsolutions.co.uk/publications/cardiff.pdf