Efficacy of Ticagrelor vs Clopidogrel in High-risk NSTE-ACS Patients Undergoing Early PCI

Overview

The goal of acute coronary syndrome (ACS) therapy is to successfully restore both epicardial blood flow and myocardial perfusion. Percutaneous coronary intervention (PCI) has been documented as being the most effective method for restoration of epicardial blood flow. However, epicardial blood flow does not necessarily equate to myocardial perfusion. Clopidogrel binds irreversibly to platelet P 2 Y 12 receptors to inhibit platelet aggregation, with main limitations of slow onset, prevention of recovery of platelet functions, and interindividual variability. Clinical pharmacology and early dose-finding studies suggested a faster onset and greater and more consistent inhibition of platelet aggregation (IPA) with ticagrelor compared with clopidogrel. Two currently main methods of angiographic assessment of myocardial perfusion includes thrombolysis in myocardial infarction(TIMI) myocardial perfusion grading (TMPG) and myocardial blush grading (MBG). These established myocardial perfusion parameters have been widely used in various important trials and are reported to be highly useful in predicting clinical outcomes. However, visual assessment of these methods is categorical, subjective, and operator dependent of contrast in the myocardium using cine-angiographic frame-counting, was developed by the investigators' center to quantify myocardial tissue- level perfusion and was proved to be a predictive value on clinical prognosis. Thus, the investigators aim to initiate an open-label study evaluating the acute efficacy of treatment with ticagrelor versus clopidogrel on myocardial tissue-level perfusion assessed by Myocardial Perfusion Frame Count(TMPFC) and magnetic resonance imaging (MRI) in patients with high-risk non-ST elevation acute coronary syndrome (NSTE-ACS) undergoing early percutaneous coronary intervention (PCI) . The investigators hypothesize that compared with clopidogrel, ticagrelor can significantly improve myocardial perfusion assessed by Myocardial Perfusion Frame Count(TMPFC) in high-risk non-ST elevation acute coronary syndrome (NSTE-ACS) patients undergoing early percutaneous coronary intervention (PCI), without additional increased major bleeding.

The goal of acute coronary syndrome (ACS) therapy is to successfully restore both epicardial blood flow and myocardial perfusion. Percutaneous coronary intervention (PCI) has been documented as being the most effective method for restoration of epicardial blood flow. However, epicardial blood flow does not necessarily equate to myocardial perfusion; not every patient with thrombolysis in myocardial infarction(TIMI) 3 flow after successful percutaneous coronary intervention (PCI) achieves effective myocardial tissue-level perfusion. Although epicardial thrombolysis in myocardial infarction(TIMI) 3 flow could be restored in \>90% of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) , normalization of myocardial perfusion was achieved less frequently, with detrimental impacts on survival. Clopidogrel, the most widely used antiplatelet agent in acute coronary syndrome (ACS), is a thienopyridine prodrug, which is inactive until in undergoes biotransformation into its active metabolite, which then binds irreversibly to platelet P 2 Y 12 receptors. This irreversible binding means that the receptors are inhibited for the lifespan of the platelet. The main limitations of clopidogrel administration include slow onset, prevention of recovery of platelet functions, and interindividual variability. Clinical pharmacology and early dose-finding studies suggested a faster onset and greater and more consistent inhibition of platelet aggregation (IPA) with ticagrelor compared with clopidogrel. ONSET/OFFSET study showed that in patients with stable coronary artery disease on aspirin, ticagrelor demonstrates a rapid onset of pharmacological effect, as demonstrated by a mean platelet aggregation (IPA) for ticagrelor at 0.5 h after 180 mg loading dose of about 41%, with the maximum platelet aggregation (IPA) effect of 87.9-89.6% by 2-4 hours post dose. A total of 90% of patients had final extent Inhibition of platelet aggregation (IPA) \>70% by 2 h post-dose. The high inhibition of platelet aggregation (IPA) effect of ticagrelor (between 87% and 89%) was maintained for 2-8 hours. Ticagrelor might overcome the slow-onset limitation of clopidogrel and bring extra benefit for improving myocardial perfusion in the acute phase of acute coronary syndrome (ACS) when undergoing early percutaneous coronary intervention (PCI). Currently, there are two main methods of angiographic assessment of myocardial perfusion: Thrombolysis in myocardial infarction (TIMI) myocardial perfusion grading (TMPG), described by Gibson et al. and myocardial blush grading (MBG), described by Van't Hof et al. These established myocardial perfusion parameters, myocardial perfusion grading (TMPG), and myocardial blush grading (MBG), have been widely used in various important trials and are reported to be highly useful in predicting clinical outcomes. However, visual assessment of these methods is categorical, subjective, and operator dependent. Thrombolysis in myocardial infarction(TIMI) Myocardial Perfusion Frame Count (TMPFC), a novel and objective method that measures the filling and clearance of contrast in the myocardium using cine-angiographic frame-counting, was developed by the investigators' center to quantify myocardial tissue- level perfusion and was proved to be a predictive value on clinical prognosis. Thus, the investigators aim to initiate an open-label study evaluating the acute efficacy of treatment with ticagrelor versus clopidogrel on myocardial tissue-level perfusion assessed by Myocardial Perfusion Frame Count (TMPFC) and magnetic resonance imaging (MRI) in patients with high-risk non-ST elevation acute coronary syndrome (NSTE-ACS) undergoing early percutaneous coronary intervention (PCI).