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

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.