title: Onset of optimal P2Y12-ADP receptor blockade after ticagrelor and prasugrel intake in Non-ST elevation acute coronary syndrome.
abstract: Pretreatment with a loading dose (LD) of clopidogrel or ticagrelor before percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) is supported by the guidelines, but debated following a recent meta-analysis on clopidogrel pretreatment and the ACCOAST trial. In this trial prasugrel pretreatment failed to reduce ischaemic events. The timing of optimal platelet reactivity (PR) inhibition of ticagrelor and prasugrel in non ST-elevation ACS (NSTE ACS) is yet undetermined. In the present study, we aimed to investigate the delay required to reach optimal PR inhibition in NSTE ACS following a LD of ticagrelor or prasugrel. Consecutive patients undergoing PCI for NSTE ACS were randomised in this monocentre study. The Vasodilator-phosphoprotein index (VASP) was used to measure PR before the LD and then at 30 minutes, 1, 2, 4 and 24 hours (h) post-LD. Optimal PR inhibition was defined as a VASP < 50%. We randomised 24 patients to ticagrelor or prasugrel LD. One hour after the LD, 29% of patients had a VASP > 50% (ticagrelor and prasugrel: 25 vs 33%; p=0.7). Optimal PR inhibition was obtained 2 h after the LD in both groups (12/12 with ticagrelor and 11/12 with prasugrel). At that time, the mean VASP index was 19 ± 16% (95%CI: 12-25). Maximal PR inhibition was reached after 4 h: 11 ± 10% (95%CI: 6-15). In NSTE ACS undergoing PCI a LD of ticagrelor or prasugrel given during the procedure provides optimal P2Y12-ADP receptor blockade in 2 h and maximal inhibition within 4 h.
authors: Laurent Bonello MD, PhD, Département de Cardiologie, Hôpital universitaire Nord de Marseille, INSERM UMRS 1076, Aix-Marseille Université, Chemin des Bourrely, Marseille 13015, France, Tel.: +33 491968858, Fax: +33 491968979, E-mail: laurentbonello@yahoo.fr.
authors: Laurent
authors: L
authors: Bonello
authors: Marc
authors: M
authors: Laine
authors: Laurence
authors: L
authors: Camoin-Jau
authors: Frederic
authors: F
authors: Noirot
authors: Régis
authors: R
authors: Guieu
authors: Françoise
authors: F
authors: Dignat-George
authors: Franck
authors: F
authors: Paganelli
authors: Corinne
authors: C
authors: Frere
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000628:therapy*; D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000097:blood; D005602:France; D006801:Humans; D008840:Microfilament Proteins / Q000097:blood; D062645:Percutaneous Coronary Intervention; D010750:Phosphoproteins / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage*; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage*; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects*; D000077486:Ticagrelor; D013997:Time Factors; D016896:Treatment Outcome; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; C548576:P2RY12 protein, human; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000098662:Vasodilator-Stimulated Phosphoprotein; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine
keywords: P2Y12-ADP receptor; pretreatment; thrombosis; vasodilator-phophoprotein