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

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 450 mg plus oral ticagrelor 180 mg, or LD of aspirin 300 mg plus ticagrelor 180 mg orally. Platelet function was evaluated at baseline, 30 min, 1 h, 4 h and 24 h 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) 0.5 mM at 30 min. Secondary endpoints were the IPA at 1, 4, and 24 h 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 0.5 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 h (p = 0.01), but not at 4 and 24 h. 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