Selatogrel, a novel P2Y12 inhibitor: a review of the pharmacology and clinical development.

INTRODUCTION: Platelet P2Y12 inhibitors have a key role in reducing thrombotic complications in patients undergoing percutaneous coronary intervention (PCI) and those with acute coronary syndrome (ACS). Clopidogrel, prasugrel and ticagrelor are widely prescribed oral P2Y12 receptor antagonists, but numerous clinical and pharmacological factors can lead to impaired gastrointestinal absorption resulting in reduced antithrombotic protection. These observations underscore the need for novel compounds or routes of administration that enable more favorable pharmacokinetic and pharmacodynamic profiles while reducing the risk for thrombotic complications. AREAS COVERED: Selatogrel, formerly known as ACT-246475, is a novel, potent, reversible, and selective non-thienopyridine antagonist of the P2Y12 receptor developed for subcutaneous administration. Results from preclinical, Phase 1 and 2 studies have shown selatogrel to have rapid absorption and sustained and reversible platelet P2Y12 inhibitory effects with a larger therapeutic window compared to the oral P2Y12 inhibitors. Such findings make selatogrel a promising agent to be tested in phase 3 studies. EXPERT OPINION: Advantages of subcutaneous administration of selatogrel are fast onset of action, easy administration and the fecal excretion not requiring dose adjustment based on renal function. These characteristics may translate into an advantage in the peri-procedural setting and in emergency and/or unconscious patients. Selatogrel may represent a viable alternative to intravenous P2Y12 inhibition (i.e. cangrelor), although some aspects need to be further clarified, including side effects, how to switch to oral P2Y12 inhibitor and the association with concomitant drugs.

Intravenous antiplatelet therapies (glycoprotein IIb/IIIa receptor inhibitors and cangrelor) in percutaneous coronary intervention: from pharmacology to indications for clinical use.

Oral antiplatelet drugs are crucially important for patients with acute coronary syndrome or stable coronary artery disease undergoing percutaneous coronary intervention (PCI). In recent decades, several clinical trials have focused on reducing periprocedural ischemic events in patients undergoing PCI by means of more rapid platelet inhibition with the use of intravenous antiplatelet drugs. Glycoprotein IIb/IIIa receptor inhibitors (GPIs) block the final common pathway of platelet aggregation and enable potent inhibition in the peri-PCI period. In recent years, however, the use of GPIs has decreased due to bleeding concerns and the availability of more potent oral P2Y12 inhibitors. Cangrelor is an intravenous P2Y12 receptor antagonist. In a large-scale regulatory trial, cangrelor administration during PCI allowed for rapid, potent and rapidly reversible inhibition of platelet aggregation, with an anti-ischemic benefit and no increase in major bleeding. This article aims to provide an overview of general pharmacology, supporting evidence and current status of intravenous antiplatelet therapies (GPIs and cangrelor), with a focus on contemporary indications for their clinical use.