Abstract
BackgroundAlthough prasugrel exerts stronger antiplatelet effects compared with clopidogrel, the factors affecting platelet reactivity under prasugrel have not been fully determined. This study aimed to find the novel mechanistic differences between two thienopyridines and identify the factor that influence platelet reactivity to each drug.MethodsForty patients with stable angina who underwent elective percutaneous coronary intervention were randomly assigned to receive either prasugrel (20 mg) or clopidogrel (300 mg) as a loading dose. Platelet function (light transmission, laser light scattering, and vasodilator-stimulated phosphoprotein phosphorylation) and plasma active metabolite levels were measured after the loading dose.ResultsPrasugrel consistently inhibited adenosine diphosphate receptor P2Y12 signalling to abolish amplification of platelet aggregation. Prasugrel abolished even small platelet aggregates composed of less than 100 platelets. On the other hand, clopidogrel inhibited large aggregates but increased small and medium platelet aggregates. Diabetes was the only independent variable for determining antiplatelet effects and active metabolite concentration of prasugrel, but not clopidogrel. Sleep-disordered breathing was significantly correlated with platelet reactivity in patients who had clopidogrel.ConclusionsPrasugrel efficiently abolishes residual P2Y12 signalling that causes small platelet aggregates, but these small aggregates are not inhibited by clopidogrel. Considering the differential effect of diabetes on antiplatelet effects between these two drugs, the pharmacokinetics of prasugrel, other than cytochrome P450 metabolism, might be affected by diabetes.Trial registrationUMIN-CTR UMIN000017624, retrospectively registered 21 May 2015.
Highlights
Prasugrel exerts stronger antiplatelet effects compared with clopidogrel, the factors affecting platelet reactivity under prasugrel have not been fully determined
Most absorbed clopidogrel is hydrolysed by esterase, and only 15% is transformed into the active metabolite by two cytochrome P450 (CYP) oxidation steps [5]
This study shows the differential effect of diabetes on antiplatelet activity between clopidogrel and prasugrel
Summary
Prasugrel exerts stronger antiplatelet effects compared with clopidogrel, the factors affecting platelet reactivity under prasugrel have not been fully determined. High on-treatment platelet reactivity under clopidogrel therapy because of genetic polymorphisms in CYP2C19 and drug-interactions increases the risk of cardiovascular events after PCI [3, 4]. These limitations of clopidogrel have led to the development of alternative P2Y12 inhibitors with a rapid onset of action and consistent antiplatelet activity. Prasugrel is a new-generation thienopyridine that shows more potent inhibition of P2Y12 with rapid onset of action, and significantly reduces ischaemic events after PCI compared with clopidogrel [6, 7]. Prasugrel is effectively converted to an active metabolite by esterases followed by a single oxidation step [8]. The peak plasma concentration of prasugrel is reached at 30 min after
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
