title: Ticagrelor vs clopidogrel followed by ticagrelor re-loading in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: A randomized, pharmacodynamic comparison.
abstract: Among patients allocated to ticagrelor in the primary percutaneous coronary intervention (PCI) cohort of Platelet Inhibition and Patient Outcomes (PLATO) trial, 40.7% had received pre-randomization 600 mg of clopidogrel. This scenario is frequently employed in real-world practice. In a prospective, three-center, single-blind, parallel design study, 74 P2Y12 inhibitor-naive patients undergoing primary PCI were randomized (Hour 0) to ticagrelor 180 mg loading dose (LD) vs clopidogrel 600 mg LD followed after 2 h by ticagrelor 180 mg re-LD. Platelet reactivity (VerifyNow, in PRU) was assessed at Hour 0, 2, 4, 6, and 24. The primary comparison was non-inferiority of ticagrelor to clopidogrel followed by ticagrelor re-LD regarding platelet reactivity at 24 h using a prespecified margin of <35 PRU for the upper bound of the one-sided 97.5% confidence interval (CI). Ticagrelor was proven non-inferior to clopidogrel followed by ticagrelor re-LD with a difference between arms of 13.5 PRU (28.8 upper 97.5% CI), p = 0.001. At Hour 2, platelet reactivity was lower in ticagrelor only vs clopidogrel followed by ticagrelor re-LD groups with least square estimate mean difference (95% CI) -105.7 (-140.6 to -70.8), p < 0.001, without significant difference thereafter. In conclusion, in patients undergoing primary PCI, a strategy of ticagrelor LD only was proven non-inferior to clopidogrel LD followed by ticagrelor re-LD, in terms of antiplatelet efficacy at 24 h post-randomization and provided an earlier onset of platelet inhibition.
authors.affiliation: a Department of Cardiology , Patras University Hospital , Rion , Patras , Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Alexopoulos
authors.affiliation: a Department of Cardiology , Patras University Hospital , Rion , Patras , Greece.
authors.forename: Kosmas
authors.initials: K
authors.lastname: Kontoprias
authors.affiliation: a Department of Cardiology , Patras University Hospital , Rion , Patras , Greece.
authors.forename: Vasileios
authors.initials: V
authors.lastname: Gkizas
authors.affiliation: b Department of Cardiology , Konstantopoulio General Hospital , Athens , Greece.
authors.forename: Stavros
authors.initials: S
authors.lastname: Karanikas
authors.affiliation: c First Cardiology Department , AHEPA University Hospital , Thessaloniki , Greece.
authors.forename: Antonios
authors.initials: A
authors.lastname: Ziakas
authors.affiliation: a Department of Cardiology , Patras University Hospital , Rion , Patras , Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Barampoutis
authors.affiliation: a Department of Cardiology , Patras University Hospital , Rion , Patras , Greece.
authors.forename: Grigorios
authors.initials: G
authors.lastname: Tsigkas
authors.affiliation: a Department of Cardiology , Patras University Hospital , Rion , Patras , Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Koutsogiannis
authors.affiliation: a Department of Cardiology , Patras University Hospital , Rion , Patras , Greece.
authors.forename: Periklis
authors.initials: P
authors.lastname: Davlouros
authors.affiliation: b Department of Cardiology , Konstantopoulio General Hospital , Athens , Greece.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Patsilinakos
authors.affiliation: c First Cardiology Department , AHEPA University Hospital , Thessaloniki , Greece.
authors.forename: Haralambos
authors.initials: H
authors.lastname: Karvounis
authors.affiliation: a Department of Cardiology , Patras University Hospital , Rion , Patras , Greece.
authors.forename: George
authors.initials: G
authors.lastname: Hahalis
authors.affiliation: a Department of Cardiology , Patras University Hospital , Rion , Patras , Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Xanthopoulou
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015415:Biomarkers; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D000077144:Clopidogrel; D004562:Electrocardiography; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis* / Q000628:therapy*; D062645:Percutaneous Coronary Intervention / Q000379:methods; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010979:Platelet Function Tests; D012307:Risk Factors; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: Angioplasty; myocardial infarction; pharmacology; platelets