Key result
Prasugrel metabolite plus GPIIb-IIIa inhibitors yields greater platelet inhibition than either agent alone.
Why the study?
Does the combination of prasugrel active metabolite and GPIIb-IIIa antagonists improve inhibition of platelet activation and aggregation in healthy donor blood?
Does the combination of prasugrel active metabolite and GPIIb-IIIa antagonists improve inhibition of platelet activation and aggregation in healthy donor blood?
p-value: p=<0.0001
Combining prasugrel with GPIIb-IIIa antagonists provides additive antiplatelet and antithrombotic effects in vitro, suggesting potential clinical benefit for high-risk PCI.
Supports additive in vitro platelet inhibition; hypothesis-generating for dual-pathway targeting in PCI, pending clinical trials.
BACKGROUND: New antiplatelet agents that provide greater, more consistent inhibition of the platelet ADP receptor P2Y12 may be used in combination with glycoprotein (GP) IIb-IIIa antagonists, but their combined effect on platelet function and procoagulant activity is not well studied. Therefore, the objective of this study was to evaluate the independent and complementary effects of P2Y12 and GPIIb-IIIa inhibition on platelet function and procoagulant activity. METHODS AND RESULTS: Healthy donor blood was treated with the active metabolite of prasugrel (R-138727 5 μmol/L), GPIIb-IIIa antagonists (abciximab 3 μg/mL or eptifibatide 0.9 μg/mL), and combinations thereof, exposed to physiologically relevant agonists (collagen and ADP) and then evaluated for markers of platelet activation and procoagulant activity. Significant interactions between R-138727 and GPIIb-IIIa antagonists were observed. R-138727 and the GPIIb-IIIa antagonists had additive inhibitory effects on collagen-stimulated platelet aggregation and on the collagen plus ADP-stimulated level of activated platelet surface GPIIb-IIIa. R-138727 and abciximab each inhibited collagen plus ADP-stimulated platelet phosphatidylserine expression and prothrombin cleavage, and the combination produced greater inhibition than achieved with abciximab alone. In contrast, eptifibatide did not inhibit, but instead enhanced, collagen plus ADP-stimulated prothrombin cleavage. Addition of R-138727 reduced prothrombin cleavage in eptifibatide-treated samples, suggesting a novel mechanism for potential benefit from combined prasugrel and eptifibatide treatment. CONCLUSIONS: The complementary effects of abciximab and R-138727 on platelet activation, aggregation, and procoagulant activity suggest their combined use may, to a greater degree than with either agent alone, reduce thrombus formation in vivo.
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Berny‐Lang et al. (2013) studied Healthy volunteers (n=6). Prasugrel active metabolite (R-138727) plus GPIIb-IIIa antagonists (abciximab or eptifibatide) vs. Vehicle or individual agents alone was evaluated on ADP-induced platelet aggregation (p=<0.0001). The combination of prasugrel's active metabolite and GPIIb-IIIa antagonists resulted in significantly greater inhibition of ADP- and collagen-induced platelet aggregation than either agent alone.
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