How to test the effect of aspirin and clopidogrel in patients on dual antiplatelet therapy?

Abstract

Dual antiplatelet therapy with clopidogrel and aspirin is frequently used for the prevention of recurrent ischemic events. Various laboratory methods are used to detect the effect of these drugs administered in monotherapy, however their value in dual therapy has not been explored. Here, we determined which methods used for testing the effect of clopidogrel or aspirin are influenced by the other antiplatelet agent. One arm of the study included 53 ischemic stroke patients being on clopidogrel monotherapy showing effective inhibition of the P2Y12 ADP receptor. Laboratory tests routinely used for the detection of aspirin resistance (arachidonic acid (AA)-induced platelet aggregation/secretion, AA-induced thromboxane B2 (TXB2) production in platelet-rich plasma and VerifyNow Aspirin assay) were carried out on samples obtained from these patients. The other arm of the study involved 52 patients with coronary artery disease being on aspirin monotherapy. Methods used for testing the effect of clopidogrel (ADP-induced platelet aggregation and secretion, flow cytometric analysis of vasodilator-stimulated phosphoprotein (VASP) phosphorylation and a newly developed P2Y12-specific platelet aggregation (ADP[PGE1] test)) were performed on samples obtained from these patients. Clopidogrel monotherapy significantly inhibited AA-induced platelet aggregation and secretion, moreover, AA-induced TXB2 production was also significantly decreased. VASP phosphorylation and AA-induced platelet aggregation showed fair correlation in patients taking clopidogrel only. Clopidogrel did not inhibit the VerifyNow Aspirin test significantly. Aspirin monotherapy influenced ADP-induced platelet aggregation and secretion, but did not have an effect on VASP phosphorylation and on the ADP[PGE1] platelet aggregation test.

Relationship between pharmacokinetics and pharmacodynamics of clopidogrel in patients undergoing percutaneous coronary intervention: comparison between vasodilator‐stimulated phosphoprotein phosphorylation assay and multiple electrode aggregometry

“…The observation that MEA correlated well with the concentrations of CAM added in vitro to fractions of the same blood sample from healthy volunteers, validates our hypothesis that wide individual variations in the many factors that influence the complex mechanism of platelet aggregation are responsible for the lack of correlation between clopidogrel PK and MEA. This is consistent with previous studies showing a strong correlation between VASP and ADP‐induced platelet aggregation when P2Y 12 inhibitors were tested in vitro or in animal models , and with other studies showing a weaker correlation in the ex vivo studies performed in patients with cardiovascular or cerebrovascular disease . Therefore, as already shown in the case of aspirin , platelet aggregation may be inadequate to specifically assess the bioavailability of the antiplatelet agents, although this functional test is sensitive to their activity.…”

High On-Treatment Platelet Reactivity in Danish Hyper-Acute Ischaemic Stroke Patients

“…Furthermore, this system can evaluate the clopidogrel response in patients receiving dual anti-platelet treatment with clopidogrel and ASA (24). …”

Impact of CYP2C19 Polymorphism on Antiplatelet Potency of Prasugrel 5 and 10 mg Daily Maintenance

“…In general, higher-speed centrifugation may be required for plasma preparation to avoid cell contamination, which was not assessed in the current study. With regard to the methodology for assessing platelet activity, we applied 3 conventional methods; however, further studies may add the VASP assay to avoid the impact of aspirin, and measure the true potency of the P2Y12 inhibitor [35]. Nonetheless, the strengths of our study were the relatively large sample size, monogenetic population, uniformed enrollment rules, single-center setup, and considerably delayed assessment in the maintenance phase.…”