Ticagrelor does not affect left ventricular remodeling following acute myocardial ischemia

Abstract

Background: Despite ticagrelor’s proven superiority to clopidogrel in treating patients with acute coronary syndrome, it is unclear whether its actions are mediated by antiplatelet inhibition or by some other pleotropic effect. In this study, we used a porcine model of acute myocardial infarction (AMI) to evaluate the efficacy of ticagrelor administered at a similar level of platelet inhibition to that seen with clopidogrel. Methods: Twenty pigs were grouped according to the P2Y12-receptor inhibitors (ticagrelor or clopidogrel). Platelet inhibition was monitored by measuring adenosine diphosphate - induced platelet aggregation. A chronic ischemic heart model was artificially generated by embolization of the middle left anterior descending coronary artery. Animals received a maintenance dose of the antiplatelet agents. Two-dimensional echocardiography was performed on the surviving animals 2 weeks later. Results: Both 180 mg ticagrelor and 600 mg clopidogrel exerted a significant and consistent antiplatelet effect showing platelet aggregation inhibition of 50.7±22.9% and 45.5±21.0%, respectively, p=0.614), which persisted for up to 2 weeks. However, no significant differences were observed in ventricular arrhythmia (40% vs. 50%, respectively; p=0.886). The ejection fraction measured 2 weeks after surgery was 44.6±7.4% in the ticagrelor group and 36.9±5.7% in the clopidogrel group (p=0.091). Conclusions: In a chronic ischemic heart failure model with a similar level of platelet inhibition, ticagrelor was no better than clopidogrel in reducing mortality and improving cardiac function.