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antiplatelet table

Antiplatelet Therapy Timeline

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In patients with AMI, ASA + streptokinase reduced 5-week vascular mortality by 40%. ASA alone – 20%, Streptokinase alone – 23% ISIS-2

Clopidogrel > ASA in reducing CV outcomes as secondary prevention in patients with prior CVA or MI. CAPRIE

In patients with NSTEMI/UA, DAPT with ASA+Clopidogrel reduces MACE but increased rate of major bleeding CURE

In high risk patients for CV events, ASA + clopidogrel did not reduce rates of MI, stroke, or death from CV causes; there was an increase in bleeding noted CHARISMA

In patients with ACS and scheduled PCI, prasugrel > clopidogrel for MACE but increases rates of major bleeding TRITON-TIMI-38

In patients with ACS, Ticagrelor > clopidogrel with reduction in MACE without increase in major bleeding PLATO

In patients who finished 1 year of DAPT after PCI with DES, continued DAPT, reduces the rate of stent thrombosis and death, MI, or stroke; more bleeding was noted DAPT

Ticagrelor monotherapy after 1 month of DAPT outperforms 12-month DAPT (aspirin and ticagrelor) after PCI for reducing clinically meaningful bleeding; no increased thrombotic risk was noted ULTIMATE-DAPT

Table 1. Antiplatelet drugs, launch date, and associated trials

Drug NameYear Launched
in the USA		Important Trials
Aspirin1897ISIS-2, GISSI
Clopidogrel1998CAPRIE, CURE
Ticagrelor2011PLATO
Prasugrel2009TRITON-TIMI-38
Cangrelor2015CHAMPION trials

Table 2. Antiplatelet drugs and pharmacodynamics

AspirinClopidogrelPrasugrelTicagrelorCangrelor
ClassCOX-InhibitorThienopyridineThienopyridineCyclopentyl-triazolopyrimidineNon-thienopyridine
Receptor BindingIrreversible P2Y12 ReceptorIrreversible P2Y12 ReceptorIrreversible P2Y12 ReceptorReversible P2Y12 ReceptorReversible P2Y12 Receptor
Half-life20 min[1]6 hours7 hours8 hours3-6 min
Onset1-2 hours2-6 hours30 min30 min2 min
Duration7-10 days3-5 days7-10 days3-5 days1 hour
MetabolismLiverLiverLiverLiverDephosphorylation
Loading Dose325mg600 mg60 mg180 mg30 mcg/kg bolus
Maintenance Dosing81mg75 mg daily10 mg daily90 mg bid4 mcg/kg/min

Additional Thoughts

  • Prasugrel is contraindicated for use in patients with prior TIA or stroke. Recommendation Class III (Harm).
  • Ticagrelor can be used in most AMI populations. Ticagrelor is more beneficial to clopidogrel in patients with diabetes mellitus. This was noted in subgroup analyses of the PLATO trial. [James, et al.,]
    • “Ticagrelor demonstrated similar in-vivo effects on platelet activation and aggregation regardless of diabetes status in patients presenting with AMI.” [Singam, et al.]
  • “A loading dose of a P2Y12 receptor inhibitor should be given as early as possible or at the time of primary PCI to patients with STEMI.” Recommendation Class, 1 LOE: B. [2013 ACC/AHA Guidelines – STEMI]
    • A discussion with an interventional cardiologist before administration is always helpful. Loading may complicate coronary artery bypass grafting timing in select individuals who may need urgent surgery.
  • Aspirin should be given to everyone with suspicion of acute myocardial infarction. Recommendation Class I, LOE B.

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