**1. Introduction**

Dual antiplatelet therapy (DAPT) consists of the combination of aspirin and an inhibitor of the platelet P2Y12 receptor for adenosine diphosphate (ADP). At the end of the 1990s, two randomized trials definitively established DAPT with aspirin and ticlopidine as the gold standard therapy after percutaneous coronary intervention (PCI) with stent implantation, in comparison to aspirin or to aspirin and anticoagulant therapy [1,2]. Ticlopidine was soon replaced by clopidogrel at the beginning of the 2000s. DAPT has proven to be among the most investigated treatments in cardiovascular medicine. Such necessity of research initially arose from the observations of late and very late stent thrombosis (ST) events occurring after first-generation drug-eluting stent (DES) implantation, highlighting lack of efficacy of clopidogrel as one of the possible drivers of thrombotic events [3] and paving the way to development of potent oral agents such as prasugrel [4] and ticagrelor [5]. More recent evidence in high-risk patients has suggested that DAPT reduces the long-term risk of cardiovascular death, spontaneous myocardial infarction (MI), stroke and major adverse cardiac events (MACE) [6,7]. After decades of research, DAPT has been moving from a stent-related to a systemic treatment among other secondary prevention strategies such as lipid-lowering therapy and control of diabetes and hypertension. Most evidence remains largely based on post-PCI patients [8], while patients that are either medically managed (e.g., those with MINOCA [9], spontaneous coronary artery dissection [10], or takotsubo syndrome [11]) or undergoing coronary artery bypass grafting (CABG) [12] remain underrepresented in clinical trials. On this background, we will discuss the role,

**Citation:** Alagna, G.; Mazzone, P.; Contarini, M.; Andò, G. Dual Antiplatelet Therapy with Parenteral P2Y12 Inhibitors: Rationale, Evidence, and Future Directions. *J. Cardiovasc. Dev. Dis.* **2023**, *10*, 163. https:// doi.org/10.3390/jcdd10040163

Academic Editor: Krishnaraj Sinhji Rathod

Received: 12 March 2023 Revised: 4 April 2023 Accepted: 7 April 2023 Published: 9 April 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

indications, and utilization of cangrelor, the only parenteral P2Y12 inhibitor available so far, its recommendations as a bridging antiplatelet agent for cardiac and non-cardiac surgery and the future directions of DAPT with new parenteral agents.
