P2Y12 receptor inhibitors: An evolution in drug design to prevent arterial thrombosis.

P2Y12 receptor inhibitors: An evolution in drug design to prevent arterial thrombosis.

Expert Opin Drug Metab Toxicol. 2018 Jan 17;:

Authors: Kupka D, Sibbing D

Abstract
INTRODUCTION: P2Y12 inhibitors are a critical component of dual antiplatelet therapy (DAPT) - a combination of a P2Y12 receptor inhibitor and aspirin - which is the superior strategy to prevent arterial thrombosis in patients with acute coronary syndromes (ACS) and undergoing stent implantation. Areas covered: Basic science articles, clinical studies, and reviews from 1992-2017 were searched using Pubmed library to collet impactful literature. After an introduction to the purinergic receptor biology, this review summarizes current knowledge on P2Y12 receptor inhibitors including their specific pharmacodynamic as well as pharmacokinetic and drug interaction features. Furthermore, we describe the subsequent improvements of next-generation P2Y12 receptor inhibitors facing the ambivalent problem of bleeding events versus prevention of arterial thrombosis in a variety of clinical settings. Therefore, we summarize data from relevant preclinical and clinical trials of currently approved P2Y12 receptor inhibitors (clopidogrel, prasugrel, ticagrelor, cangrelor) and provide strategies of drug switching and management of bleeding events. Expert Opinion: An enormous amount of pharmacologic and clinical data is available for the application of P2Y12 receptor inhibitors. Today prasugrel, ticagrelor and clopidogrel (if potent agents are contraindicated or not available) are the standard of care drugs during dual antiplatelet therapy for ACS patients, but have considerable rates of bleeding. Recent and future clinical trials will provide evidence for subsequent escalation and de-escalation strategies of P2Y12 receptor inhibition based on either adverse side effects or genetic features of each patient. These data may pave the way for an evidence-based, individualized P2Y12 receptor inhibitor therapy in ACS patients and PCI.

PMID: 29338536 [PubMed - as supplied by publisher]

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