Pharmacogenetics of the antiplatelet effect of aspirin.

The concept of "pharmacogenetics" addresses genetically determined variation in how individuals respond to drugs. Accordingly, specific genetic variants have been suggested as contributors to a reduced response to various antiplatelet drugs. Aspirin is a cornerstone in secondary cardiovascular prevention and has been thoroughly investigated. The efficacy of aspirin is well documented, although with considerable interindividual variation. According to meta-analyses, a reduced antiplatelet effect of aspirin confers an increased risk of cardiovascular events. The platelet response to aspirin is assessed by in vitro evaluation of thromboxane-dependent platelet function. A reduced antiplatelet effect of aspirin can be explained by several mechanisms, which are largely determined by clinical, pharmacodynamic, biological and genetic factors. During the past decade, numerous studies have identified genetic polymorphisms significantly associated with cardiovascular events and modulating the antiplatelet effect of aspirin. However, results have been contradictory allowing only few firm conclusions to be drawn. Polymorphisms in genes encoding glycoproteins (IIb/IIIa, Ia/IIa, VI and Ibα), cyclooxygenases (1 and 2), adenosine diphosphate receptors (P2Y1 and P2Y12) and proteins of importance for haemostasis (thromboxane A2 receptor, coagulation factor XIII, etc.) have been investigated. In particular, a polymorphism in the gene encoding glycoprotein IIb/IIIa has been associated with a reduced antiplatelet effect of aspirin. The additive value of an individual's genetic makeup in predicting the antiplatelet effect of aspirin and the risk of cardiovascular events remains controversial. The present review outlines the pharmacology of aspirin and provides an overview of specific genetic variations considered to influence the antiplatelet effect of aspirin.

Evaluation of the new INNOVANCE® PFA P2Y cartridge in patients with impaired primary haemostasis.

Recently, the INNOVANCE® PFA P2Y (P2Y) cartridge of the PFA-100® system (Siemens Healthcare Diagnostics, Marburg, Germany) has been developed for the monitoring of adenosine diphosphate (ADP) P2Y(12) receptor inhibition in patients under dual antiplatelet therapy. The aim of this study was to evaluate the influence of pre-existing defects in primary haemostasis on the P2Y cartridge independent from specific antiplatelet medication. Therefore, the closure time (CT) of the P2Y cartridge was measured in a cohort of 176 patients with assumed bleeding disorders and compared with the results of established methods for the assessment of primary haemostasis. Von Willebrand disease (VWD) was found in 25 patients (14%). The detection rate of the P2Y cartridge regarding VWD was 64% and lower compared to the two conventional cartridges (collagen/epinephrine cartridge, CEPI, 80%; collagen/ADP cartridge, CADP, 76%). In the subgroup of VWD patients with VWF:RCo < 60 IU/dL (n = 22), the correlation analysis and the inter-rater agreement revealed only limited accordance with the two established cartridges. The correlation with the CADP cartridge (C(r) = 0.767, R(2) = 0.461; Kappa = 0.41) was higher than the correlation with the CEPI cartridge. Except for severe forms, platelet function disorders (9 patients, 5%) did not prolong the CT of the P2Y cartridge. Interestingly, the P2Y cartridge was less interference-prone to unspecific medications (23 patients, 13%). As the main conclusion, it must be taken into account that low von Willebrand factor activity can significantly influence the CTs of the P2Y cartridge when using it for the monitoring of antiplatelet therapy.