Abstract
Compared to clopidogrel, prasugrel has a lower incidence of ischemic events following percutaneous coronary intervention (PCI) because of an early reduction during the acute phase in P2Y12 reaction units (PRU). The objective of this study was to compare the antiplatelet effect and vascular endothelial function of both drugs during the chronic phase after PCI. Patients who had undergone PCI and were confirmed to have no restenosis by follow-up coronary angiography under dual anti-platelet therapy with clopidogrel (75 mg/day) and aspirin (100 mg/day) were randomized to either continue clopidogrel or switch to prasugrel (3.75 mg/day). At baseline, prior to randomization we determined the CYP2C19 genotype. At the baseline and 24 weeks after randomization, the P2Y12 reactivity unit (PRU) was measured using the VerifyNow™ P2Y12 assay. Endothelial function was evaluated by flow-mediated vasodilation (FMD) and reactive hyperemia peripheral arterial tonometry (RH-PAT), while and circulating CD34+/CD133+/CD45low progenitor cells were measured by flow cytometric analysis. Serum high-sensitivity C-reactive protein (hsCRP) level was also measured. The PRU was reduced significantly in the prasugrel group (P = 0.0008), especially in patients who were intermediate or poor metabolizers based on the CYP2C19 genotype (P < 0.0001). This reduction was not observed in the clopidogrel group. The number of CD34+/CD133+/CD45low cells increased in the clopidogrel group (P = 0.008), but not in the prasugrel group. The hsCRP, FMD and reactive hyperemia index measured by RH-PAT did not change in either group. Prasugrel is potentially better than clopidogrel for preventing thrombotic events, although clopidogrel may have an advantage over prasugrel in terms of preventing atherosclerotic events. Proper use of thienopyridine drugs based on the CYP2C19 genotype has promising clinical potential.
Highlights
Thienopyridines, a class of selective irreversible inhibitors of the adenosine diphosphate receptor, P2Y12, have been used widely for their antiplatelet action [1]
Baseline data for demographic and clinical characteristics were comparable in the two groups, with the exception that the incidence of hypertension and use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and calcium channel blockers were higher in the clopidogrel group
The present study demonstrated that switching from a maintenance dose of clopidogrel to that of prasugrel even during the late phase after percutaneous coronary intervention (PCI) resulted in greater inhibition of platelet reactivity, demonstrated as a reduction in the P2Y12 reaction units (PRU) value
Summary
Thienopyridines, a class of selective irreversible inhibitors of the adenosine diphosphate receptor, P2Y12, have been used widely for their antiplatelet action [1]. Heart and Vessels (2021) 36:442–451 with Ischemic Heart Disease in Long-Term Clinical Practice (PRASFIT-Practice II) [6], showed long-term effectiveness and safety of prasugrel at dosages approved in Japan for the treatment of coronary artery disease patients undergoing PCI. To improve long-term ischemic outcomes it is necessary to prevent late thrombosis and late restenosis (late catch-up) [7], neoatherosclerosis [8] and impaired vascular healing [9] of the target lesion. It has been suggested that thienopyridines have direct pleiotropic anti-atherosclerotic effects independent of their anti-platelet action, including improvement of vascular endothelial function [11], an antiinflammatory action [12] and reduction of oxidative stress [13]
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