Tailoring Bleeding Reduction Approaches in Patients Undergoing Percutaneous Coronary Interventions: Comparative Pharmacodynamic Effects of Potent P2Y12 Inhibitor Monotherapy Versus Dual Antiplatelet Therapy De-escalation

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor represents the standard of care for the prevention of atherothrombotic events in patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). In particular, in ACS patients undergoing PCI, DAPT is initiated during the index event and maintained for up to 12 months to prevent stent-related complications as well as ischemic recurrences in non-treated coronary segments. Three oral P2Y12 inhibitors are currently recommended in this setting: clopidogrel, prasugrel, and ticagrelor. However, in ACS patients undergoing PCI, prasugrel and ticagrelor are preferred over clopidogrel based on results of large-scale clinical trials showing their superior reduction in ischemic events, including stent thrombosis. Nevertheless, such ischemic benefit occurs at the expense of increased bleeding. These observations are attributed to the greater antiplatelet potency of prasugrel and ticagrelor over clopidogrel. Importantly, accruing evidence support that bleeding complications carry significant prognostic implications, including increased mortality, underscoring the need to define antiplatelet strategies associated with reduced bleeding while preserving ischemic efficacy. The notion that most recurrent ischemic events, including stent thrombosis, occur early after the index event (i.e., 1-3 months post PCI) has prompted the design of clinical trials assessing antiplatelet treatment regimens consisting in the use of agents with enhanced platelet inhibition during the first months after PCI followed by approaches with reduced platelet inhibition. To this extent, two strategies have both proven to be effective in reducing bleeding complications while preserving efficacy compared with maintaining long-term DAPT with aspirin and a potent P2Y12 inhibitor: a) DAPT de-escalation (i.e., switching from prasugrel or ticagrelor to clopidogrel while maintaining aspirin) and b) potent P2Y12 inhibitor monotherapy (i.e., maintaining prasugrel or ticagrelor and dropping aspirin). These strategies have been tested in a number of trials and have led to changes in practice guidelines to consider either one of these strategies as bleeding reduction approaches among ACS patients undergoing PCI. However, comparative assessments between DAPT de-escalation and potent P2Y12 inhibitor monotherapy are lacking.