60  P2Y12 Inhibitors

Great review that I sourced the figure and table in Circulation. (Angiolillo et al. 2017)

60.1 Switching between Oral P2Y12 inhibitors

Consensus recommendations on switching between oral P2Y12 inhibitors. A, Switching between oral agents in the acute/early phase. In the acute/early phase (≤30 days from the index event), switching should occur with the administration of a loading dose (LD) in most cases, with the exception of patients who are de-escalating therapy because of bleeding or bleeding concerns, in whom a maintenance dose (MD) of clopidogrel (C) should be considered. Timing of switching should be 24 hours after the last dose of a given drug, with the exception of when escalating to prasugrel (P) or ticagrelor (T), when the LD can be given regardless of the timing and dosing of the previous clopidogrel regimen. *Consider de-escalation with clopidogrel 75-mg MD (24 hours after last prasugrel or ticagrelor dose) in patients with bleeding or bleeding concerns. B, Switching between oral agents in the late/very late phase. In the late/very late phase (>30 days from the index event), switching should occur with the administration of an MD 24 hours after the last dose of a given drug, with the exception of patients changing from ticagrelor to prasugrel therapy, for whom an LD should be considered. De-escalation from ticagrelor to clopidogrel should occur with administration of an LD 24 hours after the last dose of ticagrelor (but in patients in whom de-escalation occurs because of bleeding or bleeding concerns, an MD of clopidogrel should be considered). *Consider de-escalation with clopidogrel 75-mg MD (24 hours after last prasugrel or ticagrelor dose) in patients with bleeding or bleeding concerns.

60.2 Properties of P2Y12 inhibitors

Clopidogrel Prasugrel Ticagrelor Cangrelor
Receptor Blockade Irreversible Irreversible Reversible Reversible
Prodrug Yes Yes No No
Half-life of parent drug ≈6 h <5 min 6–12 h 3–6 min
Half-life of active metabolite 30 mins Distribution half-life, 30–60 mins 8–12 h NA
Elimination half-life, 2–15 h
Binding site ADP-binding site ADP-binding site Allosteric binding site Undetermined
Administration route Oral Oral Oral Intravenous
Frequency Once daily Once daily Twice daily Bolus plus infusion
Onset of action† 2–8 h 30 min–4 h 30 min–4 h ≈2 min
Offset of action 5–10 d 7–10 d 3–5 d 60 min
CYP drug interaction‡ CYP2C19 No CYP3A No
Approved settings ACS (invasive and noninvasively managed), stable CAD, PCI, PAD, and ischemic stroke ACS undergoing PCI ACS (invasive or noninvasively managed) or history of MI PCI in patients with or without ACS

60.3 Oral P2Y12 inhibitors

  • Pearls

    • Clopidogrel

      • CYP2C19 polymorphisms

      • 600 mg loading dose for immediate PCI

      • 300 mg loading dose for delayed or post-fibrinolytic PCI

    • Ticagrelor

      • Dyspnea and ventricular pauses

      • 60 mg BID is reasonable for pts extending Tx beyond 12 months

    • Prasugrel

      • Do not use for medically managed ACS

      • For PCI: load after angiography (but before the guidewire crosses the lesion)

      • Contraindicated in pts w/ hx of Stroke/TIA

      • 5 mg daily is reasonable for pts ≤ 60 kg or ≥ 75 yo

      • Generic drug

Comparison of Oral P2Y~12~ Inhibitors
Clopidogrel (Plavix) Ticagrelor (Brillinta) Prasugrel (Effient)
Loading dose 300 mg/600 mg 180 mg 60 mg
Maintenance Dose 75 mg daily 90 mg or 60 mg BID 10 mg or 5 mg daily
Binding Site ADP Allosteric ADP
Platelet Inhibition Irreversible Reversible Irreversible
Pro-Drug Yes No Yes
Metabolism Hepatic (CYP2C19) to active drug Hepatic (CYP3A4) to active metabolite Hepatic (CYP3A5/2B6) to active metabolite
Half-Life <5 mins 6-12 hrs <5 mins
Onset of Action 2-8 hrs 30 min-4 hrs 30 min-4hrs
Offset of Action 5-10 days 3-5 days 7-10 days
Clinical Pearls Genetically-mediated dose response (CYP2C19) ASA doses > 100 mg/d ↓ effectiveness of ticagrelor Contraindicated in pts w/ hx of TIA/stroke