A Critical Appraisal of the Functional Evolution of P2Y12 Antagonists as Antiplatelet Drugs

S. M.A. Fayaz, G. K. Rajanikant

Abstract

P2Y12 receptor mediated inhibition of platelet aggregation is one of the most explored and exploited pathways in antiplatelet drug therapy to prevent ischemic events in patients undergoing percutaneous coronary intervention (PCI) for the treatment of the acute coronary syndrome (ACS). Ticlopidine, Clopidogrel, Prasugrel, Ticagrelor, Cangrelor and Elinogrel are the P2Y12 inhibitors that act as antiplatelet drugs. In this review, the features of these drugs and the factors reported to be responsible for drug resistance or drug ineffectiveness were described. The features like drug metabolism, reversible or irreversible binding of drugs to their target protein and the mode of administration were observed to evolve along with the antiplatelet drugs. These features also include the drug-drug interactions, the pharmacogenetics and pharmacodynamics of P2Y12 inhibitors. We attempted to critically analyze how the desirable features were met by the P2Y12 inhibitors in the course of time. This review provides an overview of the evolution of P2Y12 inhibitors and may guide the researchers to develop better antiplatelet drugs in the future.

Keywords: Antiplatelet drugs, drug-drug interactions, P2Y12 inhibitors, pharmacogenetics, pharmacodynamics, platelet aggregation, acute coronary syndrome (ACS), Cangrelor, Elinogrel, thrombus growth