Prasugrel

• clopidogrel is an effective inhibitor of platelet activation and aggregation because of its selective and irreversible blockade of the P2Y12 receptor
  • antiplatelet therapy with clopidogrel is an important treatment for patients with acute coronary syndromes (ACS) and those undergoing percutaneous interventions when stents are used. Despite its proven benefit, clinical trials have demonstrated that decreased responsiveness or heightened platelet reactivity to clopidogrel therapy is associated with an increased risk of thrombotic events, including stent thrombosis and major adverse cardiac events
• prasugrel (1,2)
  • a third-generation thienopyridine antiplatelet agent that, like clopidogrel, exerts its antiplatelet effect by P2Y12 receptor blockade
  • treatment with prasugrel results in higher and more consistent levels of platelet inhibition than standard- or higher-dose clopidogrel
    • has several advantages compared with clopidogrel including a more rapid and efficient generation of an active metabolite, leading to a faster onset of action, a greater potency in the inhibition of adenosine-induced platelet aggregation, also a more consistent antiplatelet response without the unresponsiveness or hyporesponsiveness to clopidogrel
• in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial 38 (TRITON-TIMI), treatment with prasugrel compared with clopidogrel resulted in a 19% lower incidence in cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke but with more bleeding among patients with ACS in whom PCI was planned
  • subjects with DM tended to have a greater reduction in ischemic events without an observed increase in TIMI major bleeding and therefore a greater net treatment benefit with prasugrel compared with clopidogrel. These data demonstrate that the more intensive oral antiplatelet therapy provided with prasugrel is of particular benefit to patients with DM (2)
• in patients with STEMI undergoing PCI, prasugrel is more effective than clopidogrel for prevention of ischaemic events, without an apparent excess in bleeding (3)
• NICE (4) suggest that:
  • prasugrel 10 mg in combination with aspirin is recommended as an option within its marketing authorisation, that is for preventing atherothrombotic events in adults with acute coronary syndrome (unstable angina [UA], non-ST segment elevation myocardial infarction [NSTEMI] or ST segment elevation myocardial infarction [STEMI]) having primary or delayed percutaneous coronary intervention

Reference:

• 1.Acikel S et al. The treatment of clopidogrel resistance: Triple antiplatelet therapy and future directions International Journal of Cardiology 2009.
• 2. Wiviott SD et al. Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-Thrombolysis in Myocardial Infarction 38.Circulation. 2008 Oct 14;118(16):1626-36
• 3. Montalescot G et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet. 2009 Feb 28;373(9665):723-31.
• 4. NICE (July 2014).Prasugrel with percutaneous coronary intervention for treating acute coronary syndromes