Effects of intravenous lysine acetylsalicylate versus oral aspirin on platelet responsiveness in patients with ST-segment elevation myocardial infarction: the ECCLIPSE-STEMI trial.

Abstract

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. Recently, we demonstrated in healthy volunteers that the administration of intravenous LA resulted in a significantly reduction of platelet reactivity compared to oral aspirin. Loading dose of LA achieves platelet inhibition faster, and with less variability than aspirin. However, there are no data of this issue in patients with an ST-segment elevation myocardial infarction (STEMI). This is a prospective, randomized, multicenter, open platelet function study conducted in STEMI patients. Subjects 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, 30min, 1h, 4h and 24h using multiple electrode aggregometry and vasodilator-stimulated phosphoprotein phosphorylation (VASP). The primary endpoint of the study is the inhibition of platelet aggregation (IPA) after arachidonic acid (AA) 0.5mM at 30min. Secondary endpoints were the IPA at 1, 4, and 24h after AA, and non-AA pathways through the sequence (ADP and TRAP). A total of 32 STEMI patients were randomized (16 LA, 16 aspirin). The inhibition of platelet aggregation after AA 0.5mM at 30min was greater in subjects treated with LA compared with aspirin: 166 vs. 412 respectively (p = 0.001). This differential effect was observed at 1h (p = 0.01), but not at 4 and 24h. Subjects treated with LA presented less variability and faster inhibition of platelet aggregation wit AA compared with aspirin. 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.Trial Registration: Unique identifier: NCT02929888; URL: http://www.clinicaltrials.gov.