Temporal Trends and Predictors of P2Y12 Inhibitor Selection and Switching Following Percutaneous Coronary Intervention in Acute Coronary Syndrome Patients

INTRODUCTION: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is standard care after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). While ticagrelor provides potent ischemic protection, bleeding risk, tolerability, and treatment access may influence real-world P2Y12 inhibitor selection and ticagrelor-to-clopidogrel switching. Contemporary data describing P2Y12 inhibitor selection and recorded switching patterns across ACS subtypes remain limited. METHODS: We conducted a retrospective cohort study using the TriNetX electronic health record database to identify adults hospitalized with ACS who underwent PCI between 2013 and 2021. Patients initiating ticagrelor or clopidogrel within 14 days post-PCI were included and categorized by initial P2Y12 inhibitor. Temporal trends were assessed annually. Multivariable logistic regression identified predictors of ticagrelor initiation. Among ticagrelor initiators, switching to clopidogrel within 365 days was evaluated, including cumulative switching at prespecified landmark time points. RESULTS: Among 57,619 patients, 38.2% initiated ticagrelor and 61.8% clopidogrel. Ticagrelor initiation increased over time but remained less common overall. Ticagrelor initiation was more likely among younger patients, males, those with ST-elevation myocardial infarction, drug-eluting stent use, lower bleeding risk, and lower comorbidity burden, with substantial geographic variation observed. Among ticagrelor initiators, 31.4% had a recorded switch to clopidogrel within 1 year. Observed cumulative switching was 17.0% at 30 days, 23.0% at 90 days, 26.8% at 180 days, and 31.4% at 365 days. The median time to switch was not estimable because fewer than 50% of patients switched during follow-up. CONCLUSION: In this real-world cohort of patients with ACS undergoing PCI, initial P2Y12 inhibitor selection varied by demographic, clinical, procedural, and geographic characteristics. Recorded ticagrelor-to-clopidogrel switching was common but should not be interpreted uniformly as intentional clinical de-escalation. These findings highlight the need for future research to clarify reasons for switching and to inform individualized P2Y12 inhibitor treatment strategies in routine practice.