Ticagrelor currently represents the most tested and commonly used P2Y12 inhibitor monotherapy following percutaneous coronary intervention. The purpose of this study is to conduct a head-to-head comparison on the pharmacodynamic efficacy of ticagrelor-based and prasugrel-based single antiplatelet therapy. To determine if the PD profiles of ticagrelor- and prasugrel-based SAPT are comparable, we aim to conduct a non-inferiority study between the two strategies.

A strategy of P2Y12 monotherapy after 1-3 months of dual antiplatelet therapy (DAPT) is associated with a substantial reduction in bleeding events without an increase in atherothrombotic events, including in patients with acute coronary syndrome (ACS). However, different P2Y12 inhibitors vary in safety and efficacy profiles in the setting of single antiplatelet therapy (SAPT). In the TICO (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus-eluting Stent for Acute Coronary Syndrome) trial, DAPT discontinuation at 3 months with transition to ticagrelor monotherapy was superior to standard 12-month DAPT for 1-year net adverse cardiac events in ACS patients undergoing percutaneous coronary intervention (PCI). Similarly, the TWILIGHT (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial showed that in high-risk patients who have completed an initial 3-month course of DAPT following PCI, ticagrelor monotherapy reduced clinically meaningful bleeding events without increasing ischemic risk as compared with ticagrelor plus aspirin. In contrast, in STOPDAPT-2 ACS (Short and Optimal Duration of Dual Antiplatelet Therapy-2 Study for the Patients With ACS), discontinuation of DAPT at 1 to 2 months after ACS PCI with transition to clopidogrel monotherapy was not noninferior to 12-month DAPT with aspirin and clopidogrel for 1-year net adverse cardiac events, due to a numerical increase in atherothrombotic events despite reduction in bleeding events. These data suggest that potent P2Y12 inhibitors should be preferred over clopidogrel in the setting of early SAPT after PCI in high-risk patients.

The ISAR-REACT (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment) 5 trial showed that in ACS patients the incidence of major cardiovascular events was lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. Based on these findings, European guidelines now suggest that prasugrel should be considered in preference to ticagrelor for ACS patients who proceed to PCI. Moreover, PD studies showed that, compared with ticagrelor, prasugrel provides similar or even superior platelet inhibition [16,17]. However, this clinical PD data is in the context of using prasugrel in the context of a DAPT regimen (i.e., in adjunct to aspirin) and data on the use of prasugrel-based SAPT following PCI are limited.

Overall, these observations as well as the lack of head-to-head comparisons on the clinical and PD efficacy of ticagrelor-based and prasugrel-based SAPT underscore the importance of conducting dedicated investigations to compare these approaches. To determine if the PD profiles of ticagrelor- and prasugrel-based SAPT are comparable, we aim to conduct a non-inferiority study between the two strategies. Such investigation may provide insights into the safety and efficacy of these strategies and set the foundation for larger-scale investigations assessing clinical outcomes.

Inclusion criteria:

1. Patients on DAPT with aspirin plus prasugrel 10 mg or ticagrelor 90 mg bid as per standard of care at least 90 days after PCI.
2. Age between 18 and 75 years old
3. Able to provide written informed consent

Exclusion criteria:

1. Prior history of stent thrombosis
2. PCI within 90 days.
3. History of stroke/TIA
4. Age > 75 years old
5. Weight < 60 kg
6. History of intracranial hemorrhage
7. On treatment with any oral anticoagulant or chronic low-molecular-weight heparin (at venous thrombosis treatment, not for prophylaxis)
8. Patients with known coagulation disorders
9. Known severe hepatic impairment
10. Hypersensitivity to prasugrel or ticagrelor
11. Pregnant and breastfeeding persons [persons of childbearing age must use reliable birth control (i.e., oral contraceptives) while participating in the study]. If the potential subject is a person of childbearing potential, a pregnancy test will be done. If the subject is pregnant, participation in this study will end.