Antiplatelet therapy in acute coronary syndromes

Figures & data

Figure 1. Platelet activation mechanisms: receptors involved and their antagonists (aspirin is not a receptor blocker but an inhibitor of the formation of the receptor agonist thromboxane-A2).

Table 1. Factors influencing clopidogrel response variability.

Genetic factors	Polymorphism of CYP2C19
	Polymorphism of CYP3A4
	Polymorphism of ABCB1
	Polymorphism of PON1
Cellular factors	Reduced CYP3A metabolic activity
	Up-regulation of the P2Y12 pathway
	Up-regulation of the P2Y1 pathway
	Up-regulation of the P2Y-independent pathways
	(collagen, thromboxane-A2, thrombin)
	Increased ADP exposure
	Accelerated platelet turnover
Clinical factors	Poor compliance
	Underdosing
	Drug–drug interactions involving CYP450 isoenzymes
	Reduced intestinal absorption
	High BMI
	Diabetes mellitus
	ACS

ACS: acute coronary syndrome; ADP: adenosine diphosphate; BMI: body mass index.

Table 2. Novel antiplatelet drugs.

	Target receptor	Pro-drug	Inhibition mode	Administration route	Pivotal clinical trials	Stage of development
Prasugrel	P2Y12	Yes	Irreversible	Oral	TRITON-TIMI 38	EMA- and FDA-approved
Ticagrelor	P2Y12	No	Reversible	Oral	PLATO	EMA- and FDA-approved
Cangrelor	P2Y12	No	Reversible	Parenteral	CHAMPION-PHOENIX	Ongoing Phase III
Elinogrel	P2Y12	No	Reversible	Oral and parenteral	INNOVATE-PCI	Phase II completed
Vorapaxar	PAR-1	No	Reversible	Oral	TRACER	Phase III completed
Atopaxar	PAR-1	No	Reversible	Oral	LANCELOT	Phase II completed

EMA: European Medicines Agency; FDA: Food and Drug Administration; PAR-1: protease-activated receptor-1.

Figure 2. Major efficacy (panel A) and safety (panel B) end points after 15 months in the TRITON-TIMI 38 trial. The primary end point was the composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke. Stent thrombosis was defined as definite or probable in accordance with the Academic Research Consortium.

Figure 3. Major efficacy (panel A) and safety (panel B) end points after 12 months in the PLATO trial. The primary end point was the composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke. Stent thrombosis was defined as definite or probable in accordance with the Academic Research Consortium.