A study on platelet reactivity and associated clinical characteristics in acute coronary syndrome patients treated with Ticagrelor and Clopidogrel

ABSTRACT

Background: The pathophysiology of the acute coronary syndrome (ACS) is characterized by the rupture of an atherosclerotic plaque within the coronary artery, with subsequent platelet aggregation, thrombus formation, and ischemia. Before platelets aggregate, they must first be activated to express activated glycoprotein IIb/IIIa receptors on the cell surface. This activation is the result of stimulation from endogenous platelet agonists, such as thromboxane A2 and adenosine diphosphate (ADP). ADP activates platelets by binding to P2Y12 receptors on the cell surface. Despite clinical efficacy in a broad range of coronary artery disease patients, pharmacodynamic studies conducted in patients undergoing stenting showed that clopidogrel therapy was associated with variable and moderate platelet inhibition (50% inhibition at steady state as demonstrated by ex-vivo ADP-induced platelet aggregation) as well. Ticagrelor, a cyclopentyl-triazolo-pyrimidine acting as an analog of adenosine triphosphate (ATP), constitutes a first non-thienopyridine direct platelet P2Y12 receptor blocker. Aim of the study To investigate factors linked to HOTPR on ticagrelor and whether they differ from factors linked to HOTPR on clopidogrel. Materials and methods: Totally 300 patients were included in the study Patients presenting to the Department of Cardiology, SRM Medical College Hospital and Research Institute, Kattangulathur, Veeraraghavan Sriram, Venkatesh Munusamy, Dhandapani Vellala Elumalai. A study on platelet reactivity and associated clinical characteristics in acute coronary syndrome patients treated with Ticagrelor and Clopidogrel. IAIM, 2019; 6(8) 26- 34. Page 27 Kanchipuram District, Chennai with an ACS between January 2018 to May 2019 were eligible for inclusion in the study if coronary angiography (±PCI) was planned and they were adequately pretreated with Ticagrelor or clopidogrel and aspirin. An ACS was defined as symptoms suggestive of myocardial ischemia lasting > 15 min with either troponin elevation or new electrocardiogram (ECG) changes consistent with myocardial ischemia. ECG changes consistent with myocardial ischemia included ≥ 1 mm of ST-segment deviation or T wave inversion ≥ 1 mm in at least 2 contiguous leads. Troponin was considered elevated if greater than 14 ng/L, with a rise and/or fall of 50% if 14-50 ng/L or 20% if >50 ng/L in a subsequent measure. Results: The mean age was 63 ± 12 years with 71.9% being male and 18% having diabetes. Patients predominantly presented with NSTEMI 76% and 24% as STEMI. Patients treated with Ticagrelor were younger, more likely to be male, less likely to present with STEMI, have suffered a previous MI, experience atrial fibrillation and be taking proton pump inhibitors or calcium channel blockers. Patients who were administered Ticagrelor demonstrated significantly lower platelet reactivity when stimulated with ADP compared to patients administered clopidogrel (30.3 AU vs 43.7 AU respectively, p<0.0001). Conclusion: This study demonstrates that Ticagrelor provides more potent platelet inhibition than clopidogrel measured by MEA. This is reflected in ticagrelor’s ability to reduce the proportion of ACS patients experiencing HOTPR. Different clinical factors contribute to HOTPR in ACS patients treated with Ticagrelor or clopidogrel. Clopidogrel dose, renal insufficiency, clinical presentation, and platelet count are linked to clopidogrel HOTPR. In contrast, only a history of myocardial infarction is associated with Ticagrelor HOTPR.