*Review* **Dual Antiplatelet Therapy with Parenteral P2Y12 Inhibitors: Rationale, Evidence, and Future Directions**

**Giulia Alagna 1, Paolo Mazzone 2, Marco Contarini <sup>2</sup> and Giuseppe Andò 1,\***


**Abstract:** Dual antiplatelet therapy (DAPT), consisting of the combination of aspirin and an inhibitor of the platelet P2Y12 receptor for ADP, remains among the most investigated treatments in cardiovascular medicine. While a substantial amount of research initially stemmed from the observations of late and very late stent thrombosis events in the first-generation drug-eluting stent (DES) era, DAPT has been recently transitioning from a purely stent-related to a more systemic secondary prevention strategy. Oral and parenteral platelet P2Y12 inhibitors are currently available for clinical use. The latter have been shown to be extremely suitable in drug-naïve patients with acute coronary syndrome (ACS), mainly because oral P2Y12 inhibitors are associated with delayed efficacy in patients with STEMI and because pre-treatment with P2Y12 inhibitors is discouraged in NSTE-ACS, and in patients with recent DES implantation and in need of urgent cardiac and non-cardiac surgery. More definitive evidence is needed, however, about optimal switching strategies between parenteral and oral P2Y12 inhibitors and about newer potent subcutaneous agents that are being developed for the pre-hospital setting.

**Keywords:** dual antiplatelet therapy; P2Y12 inhibitors; acute coronary syndrome; clopidogrel; prasugrel; ticagrelor; cangrelor; selatogrel; zalunfiban
