Effects of intravenous lysine acetylsalicylate versus oral aspirin on platelet responsiveness in patients with ST-segment elevation myocardial infarction

Abstract

Abstract Background Prasugrel and ticagrelor, new P2Y12-ADP receptor antagonists, are associated with greater pharmacodynamic inhibition and reduction of cardiovascular events in patients with an acute coronary syndrome. However, evidence is lacked about the effects of achieving faster and stronger cyclooxygenase inhibition with intravenous lysine acetylsalicylate (LA) compared to oral aspirin on prasugrel inhibited platelets in patients with an ST-segment elevation myocardial infarction (STEMI). Methods This is a prospective, randomized, multicenter, open platelet function study conducted. STEMI patients were randomly assigned to receive a loading dose (LD) of intravenous LA 450mg plus oral ticagrelor 180mg, or LD of aspirin 300mg plus ticagrelor 180mg orally. Platelet function was evaluated at baseline, 30 min, 1h, and 24h using multiple electrode aggregometry and vasodilator-stimulated phosphoprotein phosphorylation (VASP). The primary endpoint of the study is the inhibition of platelet aggregation after arachidonic acid (AA) 1.5mM at 30 min. Secondary endopoints are the inhibition of platelet aggregation after AA baseline and at 1h, and 24h, and measurement of aggregation with other platelet test (ADP, collagen and VASP). Results A total of 32 STEMI patients were randomized (16 LA, 16 aspirin). The inhibition of platelet aggregation after AA 1.5 mM at 30 min was greater in subjects treated with LA compared with aspirin: 166 vs. 412 respectively, p=0.001. This differential effect was observed at 1 hour (p=0.01), but not at 24 hours. Subjects treated with LA presented less variability and faster and greater inhibition of platelet aggregation with AA compared with aspirin (Figure 1). Conclusions The administration of intravenous LA resulted in a significantly reduction of platelet reactivity compared to oral aspirin on ticagrelor inhibited platelets in patients with STEMI. Loading dose of LA achieves an earlier platelet inhibition, and with less variability than aspirin. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was supported by the CTU-SCReN (Clinical Trial Unit – Spanish Clinical Research Network) from San Carlos University Hospital (Madrid, Spain), financed by the ISCII (Project PI16/00191)