Comparative Efficacy and Safety of P2Y12 Inhibitor Monotherapy Versus Dual Antiplatelet Therapy in Patients Following...

Dual antiplatelet therapy (DAPT) is the standard approach for preventing ischemic events following percutaneous coronary intervention (PCI); however, the associated bleeding risk has led to growing interest in P2Y12 inhibitor monotherapy after an initial DAPT period. This systematic review evaluates the efficacy and safety of monotherapy with ticagrelor, clopidogrel, or prasugrel following one to three months of initial DAPT, compared to prolonged DAPT regimens. A comprehensive literature search was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, identifying randomized controlled trials (RCTs) and high-quality comparative studies published within the last five years. Study quality was assessed using the Cochrane Risk of Bias 2.0 tool for RCTs and the Newcastle-Ottawa Scale (NOS) for post-hoc analyses. Primary outcomes included major adverse cardiovascular events (MACE) and clinically significant bleeding. Monotherapy was associated with a lower incidence of major bleeding (hazard ratio (HR) range: 0.35-0.66) while maintaining comparable ischemic outcomes, with reported MACE HRs ranging from 0.54 to 1.14. Ticagrelor monotherapy showed consistent bleeding reduction, particularly in high-risk populations, whereas clopidogrel demonstrated similar cardiovascular efficacy and a favorable safety profile in select cohorts. Efficacy and safety outcomes varied across studies depending on the agent used and patient characteristics, and moderate between-study heterogeneity was observed in trial design, populations, and outcome definitions. These findings support the use of individualized antiplatelet strategies, with P2Y12 inhibitor monotherapy emerging as a viable option for reducing bleeding risk without compromising ischemic protection in appropriately selected post-PCI patients.