Prasugrel inhibits platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y12 adenosine diphosphate receptor on the platelet surface, thereby preventing the formation of clots.
The efficacy of prasugrel was compared with that of clopidogrel in a large, double-blind study involving 13,608 patients with acute coronary syndromes (ACS) with scheduled PCI who were at moderate to high risk of unstable angina, non-ST segment elevation MI (NSTEMI) or STEMI.1
Patients randomised to the prasugrel group received a 60mg loading dose followed by a maintenance dose of 10mg daily. Those in the clopidogrel group received a 300mg loading dose followed by 75mg daily. All patients were co-administered aspirin (recommended dose, 75–162mg daily) and other standard therapy. Patients were treated for a median of 14.5 months.
In the overall study population, prasugrel was associated with a significantly lower incidence of the primary composite end-point (cardiovascular death, non-fatal MI, or non-fatal stroke) than clopidogrel. A significant reduction in the primary endpoint in the prasugrel group was observed by three days and persisted throughout follow-up. The difference between the two groups was largely due to a significant reduction in MI in the prasugrel group compared with the clopidogrel group.
The incidence of major bleeding was greater in the prasugrel group than in the clopidogrel group. The study also identified three sub-groups of patients with less clinical efficacy and an increased risk of bleeding: patients with a history of stroke or TIA; patients aged 75 or over; and those weighing 60kg or less.
1. Wiviott SD, Braunwald E, McCabe CH et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001–15.
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