Clinical Drug Experience Knowledgebase

The ANTARCTIC Study - Assessment of a Normal Versus Tailored Dose of Prasugrel After Stenting in Patients Aged > 75 Years to Reduce the Composite of Bleeding, Stent Thrombosis and Ischemic Complications

Objective: To demonstrate the superiority of a strategy of platelet monitoring (Monitoring Arm) with down-adjustment of the dose of prasugrel in high responders and up-adjustment of the dose of prasugrel in low responders as compared to a more conventional strategy of a fixed dose of 5 mg to every patient without monitoring (Conventional Arm).Rationale: Prasugrel 10 mg is superior to clopidogrel in patients with acute coronary syndrome treated by percutaneous coronary intervention, reducing significantly the rates of ischemic events. Elderly patients appear to be at higher risk of bleeding events and pharmacokinetic data suggests that elderly patients are exposed to a higher concentration of the active metabolite of prasugrel. A reduced dose of 5 mg of prasugrel is therefore proposed to these patients to limit the risk of bleeding. On the other hand, the elderly have also a higher ischemic risk and higher levels of platelet aggregation under treatment than younger patients and may deserve stronger protection from antiplatelet therapy. Platelet function testing appears to be of particular interest in patients at high risk of both ischemic and bleeding events like the elderly. Too intense platelet inhibition may expose the elderly patients to an excessive bleeding risk. Too low platelet inhibition may expose them to recurrent cardiovascular ischemic events. The possibility of bedside monitoring of oral antiplatelet therapy offers the opportunity of tailoring prasugrel therapy in elderly patients to optimize their risk/benefit ratio. Such strategy has never been evaluated in a randomized and adequately powered study. Population: Acute coronary syndrome (STEMI and NSTEMI) treated by PCI-stent (bare metal stent or drug eluting stent) in patients aged 75 ≥ year. Methods: Monitoring with VerifyNow P2Y12, 2 weeks after initiation of 5 mg of maintenance dose of prasugrel, reduction of antiplatelet therapy if there is high on-treatment platelet inhibition (HPI) or increase in dosing if there is high on-treatment platelet reactivity (HPR). Patients will be monitored again 2 weeks later, only if they do not meet the Verifynow P2Y12 targets at the first assessment. Primary endpoint net clinical benefit at 12 months:Composite of Cardiovascular death, myocardial infarction, stroke, urgent revascularisation, stent thrombosis and bleedings according to the BARC definitions (type 2, 3 or 5) Centers: Approximately 40 French high volume PCI centers