INTRODUCTION: Previous work suggests that the extent of platelet inhibition by P2Y(1) receptor antagonism may be underappreciated, particularly in the context of dual antiplatelet therapy with aspirin and clopidogrel. MATERIALS AND METHODS: Using P2Y(1), P2Y(12), and TxA(2) receptor antagonists individually and in combination, we assessed the incremental changes from baseline platelet reactivity in blood collected from healthy volunteers. RESULTS: The P2Y(1) receptor antagonist further inhibited platelet activation and aggregation in several assay conditions ex vivo when combined with P2Y(12) and/or TxA(2) receptor blockers. Collagen and TRAP-induced platelet aggregation measured by light transmittance aggregometry was inhibited to a greater extent with the triple combination relative to each of the antagonists alone. The triple combination of P2Y(1), P2Y(12), and TxA(2) receptor antagonists also significantly shifted adenosine diphosphate (ADP)-stimulated platelet glycoprotein IIb/IIIa receptor and P-selectin expression compared to individual or dual antagonists. CONCLUSIONS: These results substantiate that additional platelet inhibition occurs with the triple combination of P2Y(1), P2Y(12), and TxA(2) receptor antagonists and support further testing of P2Y(1) receptor antagonists as an option for alternative, synergistic, or triple antiplatelet therapy.
INTRODUCTION: Previous work suggests that the extent of platelet inhibition by P2Y(1) receptor antagonism may be underappreciated, particularly in the context of dual antiplatelet therapy with aspirin and clopidogrel. MATERIALS AND METHODS: Using P2Y(1), P2Y(12), and TxA(2) receptor antagonists individually and in combination, we assessed the incremental changes from baseline platelet reactivity in blood collected from healthy volunteers. RESULTS: The P2Y(1) receptor antagonist further inhibited platelet activation and aggregation in several assay conditions ex vivo when combined with P2Y(12) and/or TxA(2) receptor blockers. Collagen and TRAP-induced platelet aggregation measured by light transmittance aggregometry was inhibited to a greater extent with the triple combination relative to each of the antagonists alone. The triple combination of P2Y(1), P2Y(12), and TxA(2) receptor antagonists also significantly shifted adenosine diphosphate (ADP)-stimulated platelet glycoprotein IIb/IIIa receptor and P-selectin expression compared to individual or dual antagonists. CONCLUSIONS: These results substantiate that additional platelet inhibition occurs with the triple combination of P2Y(1), P2Y(12), and TxA(2) receptor antagonists and support further testing of P2Y(1) receptor antagonists as an option for alternative, synergistic, or triple antiplatelet therapy.
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Authors: John H Alexander; Renato D Lopes; Stefan James; Rakhi Kilaru; Yaohua He; Puneet Mohan; Deepak L Bhatt; Shaun Goodman; Freek W Verheugt; Marcus Flather; Kurt Huber; Danny Liaw; Steen E Husted; Jose Lopez-Sendon; Raffaele De Caterina; Petr Jansky; Harald Darius; Dragos Vinereanu; Jan H Cornel; Frank Cools; Dan Atar; Jose Luis Leiva-Pons; Matyas Keltai; Hisao Ogawa; Prem Pais; Alexander Parkhomenko; Witold Ruzyllo; Rafael Diaz; Harvey White; Mikhail Ruda; Margarida Geraldes; Jack Lawrence; Robert A Harrington; Lars Wallentin Journal: N Engl J Med Date: 2011-07-24 Impact factor: 91.245
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