Factors Affecting Residual Platelet Aggregation in Prasugrel Treated Patients

Dimitrios      Alexopoulos; Ioanna      Xanthopoulou; Angelos      Perperis; Argyro      Siapika; Katerina      Stavrou; Evropi      Tsoni; Periklis      Davlouros; George      Hahalis

Abstract

Identification of factors affecting platelet reactivity (PR) and high PR (HPR) or high platelet inhibition (HPI) rates while on prasugrel maintenance dose (MD) might be helpful in avoiding ischemic or bleeding complications. We retrospectively analyzed all patients (n=233) treated in our institution between April 2010 and November 2012 who had platelet function assessment pre-prasugrel and following prasugrel 10 mg MD for at least 5 days, using the Verify Now P2Y12 platelet function assay. Multiple linear regression and logistic regression models were applied to identify independent factors affecting post-prasugrel PR level, HPR and HPI status. The amount of variance in PR under prasugrel MD that could be explained by the model was 25.9% (adjusted R2), p<0.001. Pre-prasugrel treatment PR, acute coronary syndrome (ACS), prasugrel loading and smoking uniquely accounted for 10.8%, 1.3%, 3.5% and 1.2% of the observed variance, respectively. HPR and HPI were observed in 7.7% and 13.7% of the cases, respectively. On multivariate analysis, pre-prasugrel PR in the upper quartile (>313 PRU) was the only independent factor associated with HPR under prasugrel MD. In contrast, pre-prasugrel PR in the lower quartile (<242 PRU) and prasugrel loading emerged as the only independent predictors of HPI.

In patients under different clinical settings receiving prasugrel 10 mg MD a significant amount of the PR variability in response to prasugrel may be explained by pre- treatment PR level, ACS, prasugrel loading and smoking status. A high pre- treatment PR is associated with HPR, while a low pre-treatment PR and prasugrel loading predict HPI.

Keywords: Prasugrel, platelet reactivity, platelet pharmacology, pharmacodynamics.

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