title: Platelet function and coagulation in patients with STEMI and peri-interventional clopidogrel plus heparin vs. prasugrel plus bivalirudin therapy (BRAVE 4 substudy).
abstract: BACKGROUND
  In this prespecified BRAVE 4 substudy we examined the antiplatelet and anticoagulant efficacy of clopidogrel plus heparin vs. prasugrel plus bivalirudin in patients with ST-segment elevation myocardial infarction.
  
  
  METHODS
  26 patients received clopidogrel/heparin, 25 patients received prasugrel/bivalirudin and 20 additional untreated patients served as controls. Platelet aggregation was tested using whole blood impedance aggregometry. Dynamic platelet adhesion and aggregate formation to collagen were quantified under flow conditions. Coagulation tests included activated partial thromboplastin time (aPTT), international normalized ratio (INR) as well as rotational thrombelastography (ROTEM®). Analyses were performed 3 and 72h after drug administration.
  
  
  RESULTS
  At 3, but not at 72h we observed a significant increase in the inhibition of platelet aggregation in response to adenosine diphosphate (P<0.01), but not to arachidonic acid, collagen or thrombin receptor agonist in the prasugrel/bivalirudin group compared to the clopidogrel/heparin group. Inhibition of platelet adhesion to collagen under flow was significantly stronger in the prasugrel/bivalirudin group at 3 and 72h after drug administration (P<0.01). APTT was significantly higher in the clopidogrel/heparin group (P<0.05) and INR was significantly higher in the prasugrel/bivalirudin group (P<0.01) 3h after drug administration. Concerning ROTEM® analysis the drug combinations did not differ in reducing clot formation time (CFT) and both combinations did not influence maximum clot firmness (MCF) compared to the controls.
  
  
  CONCLUSIONS
  We could demonstrate a more pronounced inhibition of platelet aggregation as well as platelet adhesion and aggregate formation to collagen under flow in prasugrel plus bivalirudin treated patients.
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Campus Großhadern, Munich, Germany; Munich Heart Alliance, Munich, Germany. Electronic address: Daniel.Braun@med.uni-muenchen.de.
authors.forename: Daniel
authors.initials: D
authors.lastname: Braun
authors.affiliation: Deutsches Herzzentrum München, Technische Universität München, Munich, Germany; Munich Heart Alliance, Munich, Germany.
authors.forename: Antonia
authors.initials: A
authors.lastname: Knipper
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Campus Großhadern, Munich, Germany; Munich Heart Alliance, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Orban
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Campus Großhadern, Munich, Germany; Munich Heart Alliance, Munich, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Sibbing
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Campus Großhadern, Munich, Germany; Munich Heart Alliance, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Petzold
authors.affiliation: Institut für Laboratoriumsmedizin, Deutsches Herzzentrum München, Munich, Germany.
authors.forename: Siegmund
authors.initials: S
authors.lastname: Braun
authors.affiliation: Deutsches Herzzentrum München, Technische Universität München, Munich, Germany; Munich Heart Alliance, Munich, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schulz
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Campus Großhadern, Munich, Germany; Munich Heart Alliance, Munich, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hausleiter
authors.affiliation: Deutsches Herzzentrum München, Technische Universität München, Munich, Germany; Munich Heart Alliance, Munich, Germany.
authors.forename: Adnan
authors.initials: A
authors.lastname: Kastrati
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Campus Großhadern, Munich, Germany; Munich Heart Alliance, Munich, Germany.
authors.forename: Julinda
authors.initials: J
authors.lastname: Mehilli
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Campus Großhadern, Munich, Germany; Munich Heart Alliance, Munich, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Massberg
mesh_terms: D000991:Antithrombins / Q000008:administration & dosage*; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005260:Female; D006493:Heparin / Q000008:administration & dosage; D006629:Hirudins / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D010446:Peptide Fragments / Q000008:administration & dosage; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010979:Platelet Function Tests / Q000379:methods*; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013916:Thrombelastography / Q000379:methods*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D006493:Heparin; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; C074619:bivalirudin
keywords: BRAVE 4; Coagulation; Platelet function; STEMI