The future of P2Y₁₂ receptor antagonists

Figures & data

Figure 1. The role of P2Y₁₂ receptors in platelet activation. Platelet activation is induced by collagen, thromboxane A₂, thrombin and ADP, as well as other agonists. This triggers the release of dense granules, which contain ADP. The released ADP then acts on platelet ADP receptors, of which, the P2Y₁₂ receptor has a major role in amplifying the response of the platelet to the initial agonist (highlighted in red).

Table 1. Summary of our predictions for the most successful strategies for P2Y₁₂ inhibition in the future.

	Predicted strategies for the future
Pharmacology	Use of P2Y12 inhibitors that have the following properties:
	1. Direct acting or require minimal biotransformation 2. Minimal interaction with CYP enzymes 3. Cause a level of P2Y12 inhibition that is no greater than the level currently achieved by ticagrelor and prasugrel 4. Bind reversibly 5. Antidote readily available 6. Safe and well-tolerated 7. Can be administered intravenously or can be used in conjunction with intravenous inhibitors
Clinical usage	Clinical strategies that involve:
	1. Administration of intravenous P2Y12 inhibitors or, otherwise, oral P2Y12 inhibitors prior to coronary angiography 2. Identification of patients likely to benefit from long-term P2Y12 inhibition 3. Possible increased prominence of P2Y12 inhibitors in the management of stroke and peripheral arterial disease 4. Possible new indications for P2Y12 inhibitors in stable patients with diabetes and patients with pneumonia 5. Use of P2Y12 inhibitors without aspirin in certain clinical contexts