Comparisons Among Orally Effective P2Y12 Inhibitors Clopidogrel Prasugrel Ticagrelor Pharmacology Prodrug requires conversion to active metabolite that irreversibly blocks P2Y12 receptor Prodrug requires conversion to active metabolite that irreversibly blocks P2Y12 receptor. Conversion to active metabolite occurs more rapidly and to a greater degree than with clopidogrel Parent compound is active and no biotransformation is required for reversible inhibition of P2Y12 receptor Effect on platelet aggregation There is a delay of several hours before maximal antiplatelet effect is seen Onset of antiplatelet effect is faster and extent of inhibition of aggregation is greater than with clopidogrel (a significant antiplatelet effect was observed within 30 min of loading) Onset of antiplatelet effect is faster and extent of inhibition of aggregation is greater than with clopidogrel (a significant antiplatelet effect was observed within 30 min of loading) Management strategy Conservative Invasive Conservative Invasive Conservative Invasive Loading dose 300 mg 600 mg Generally not recommended for precatheterization use in UA/NSTEMI 60 mg at time of PCI 180 mg 180 mg Timing Initiate on presentation Initiate as soon as possible before or at the time of PCI Initiate as soon as coronary anatomy is known and decision is made to proceed with PCI Initiate on presentation Initiate as soon as possible before or at the time of PCI Maintenance dose 75 mg Optimal approach to dosing in individual patients based on genotype and individual antiplatelet effects not rigorously established Optimal individual dose not rigorously established (see comment to left). (150 mg for first 6 d is an alternative) Consider reduction to 5 mg in patients weighing 60 kg. The efficacy (or benefit) of prasugrel in those age 75 y is uncertain. Contraindicated in patients with a history of stroke or TIA. 