In the presence of strong P2Y12 receptor blockade, aspirin provides little additional inhibition of platelet aggregation

Abstract

In the presence of strong P2Y 12 receptor blockade, aspirin provides little additional inhibition of platelet aggregation. J Thromb Haemost 2011; 9: 552-61.Summary. Background: Aspirin and antagonists of platelet ADP P2Y 12 receptors are often coprescribed for protection against thrombotic events. However, blockade of platelet P2Y 12 receptors can inhibit thromboxane A 2 (TXA 2 )-dependent pathways of platelet activation independently of aspirin. Objectives: To assess in vitro whether aspirin adds additional antiaggregatory effects to strong P2Y 12 receptor blockade. Methods: With the use of platelet-rich plasma from healthy volunteers, determinations were made in 96-well plates of platelet aggregation, TXA 2 production and ADP/ATP release caused by ADP, arachidonic acid, collagen, epinephrine, TRAP-6 amide and U46619 (six concentrations of each) in the presence of prasugrel active metabolite (PAM; 0.1-10 lmol L ) and PAM + aspirin, aspirin generally failed to produce more inhibition than PAM or additional inhibition to that caused by PAM. The antiaggregatory effects of PAM were associated with reductions in the platelet release of both TXA 2 and ATP + ADP. Similar effects were found when either citrate or lepirudin were used as anticoagulants, and when traditional light transmission aggregometry was conducted at low stirring speeds. Conclusions: P2Y 12 receptors are critical to the generation of irreversible aggregation through the TXA 2 -dependent pathway. As a result, strong P2Y 12 receptor blockade alone causes inhibition of platelet aggregation that is little enhanced by aspirin. The clinical relevance of these observations remains to be determined.

Standardised optical multichannel (optimul) platelet aggregometry using high-speed shaking and fixed time point readings

“…As we have previously reported in standard 96-well plate and optimul kinetic aggregometry [1,[4][5][6], we found that aspirin significantly inhibited ( p < 0.05) aggregation induced by EPI and completely abolished responses to AA and collagen. PAM, however, significantly attenuated ( p < 0.05) aggregation induced by all agonists tested, except for ristocetin, which acts through a process that involves agglutination and not aggregation.…”

Pharmacodynamic Comparison of Prasugrel Versus Ticagrelor in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease

“…In particular, the level of platelet inhibition achieved by combining aspirin and a potent P2Y 12 receptor antagonist is no greater than that produced by the P2Y 12 receptor antagonist alone. 31 Our study confirms these in vitro findings by demonstrating in vivo that potent P2Y 12 receptor blockade with both prasugrel and ticagrelor is also associated with inhibitory effects on measures of non-ADP-induced platelet reactivity. In particular, our study further expands on previous observations showing that, in DM patients, the addition of either prasugrel or ticagrelor on top of aspirin is able to significantly reduce thromboxane A 2 -mediated platelet reactivity, as assessed by assays sensitive to aspirin-induced effects (arachidonic acid-and collageninduced aggregation), and platelet reactivity mediated by thrombin, as well, in both the acute and maintenance phases of treatment.…”

Ticagrelor Compared With Clopidogrel by Geographic Region in the Platelet Inhibition and Patient Outcomes (PLATO) Trial

“…The effects of aspirin on platelet reactivity are relatively limited compared with P2Y 12 inhibition. 13 Furthermore, it has been suggested that P2Y 12 inhibition alone may partially inhibit platelet thromboxane A 2 synthesis, 14,15 and in the presence of strong P2Y 12 inhibition, the additional effects of higher aspirin doses may result in a reduction of prostacyclin release, potentially shifting the influence of aspirin to a prothrombotic effect. 16 Consistent with the Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent Events/Optimal Antiplatelet Strategy for Interventions (CURRENT/OASIS 7) trial, 17 no association of aspirin maintenance dose with ischemic event rates in the clopidogrel group was observed.…”