title: Platelet inhibition by increased tirofiban dosing during primary coronary angioplasty for ST elevation myocardial infarction.
abstract: BACKGROUND
  Platelet receptor IIb/IIIa inhibition during percutaneous coronary interventions (PCI) decreases incidence of major adverse cardiac events (MACE). These effects directly result from the level of platelet inhibition. Due to existing data indicating that standard dosing of tirofiban is insufficient for optimal platelet inhibition, we proposed a novel, experimental dosing.
  
  
  OBJECTIVE
  In this study we assessed, with the use of Ultegra Rapid Platelet Function Assay (RFPA), the level of platelet inhibition with increased tirofiban dosing during primary PCI for ST elevation myocardial infarction (STEMI).
  
  
  METHODS
  Twenty eight patients (22 males, 6 females, mean age 63 years, range 32-78 years) with STEMI were included into the study. All patients received 300 mg of aspirin, iv. heparin in a dose of 10 000 IU, which was followed by platelet receptor GP IIb/IIIa inhibitor tirofiban - 10 micro g/kg iv bolus, 0.4 micro g/kg/min for 30 min and infusion 0.1 micro g/kg/min continued for 12-24 h. Platelet function was assessed with RFPA before tirofiban administration and after 10, 30, 90 minutes as well as 8 hours from the initial dose of tirofiban. Baseline fibrinogen binding to platelet receptor IIb/IIIa was defined as PAU (platelet aggregation unit) and the effects of tirofiban on platelets were expressed as a percentage of platelet inhibition.
  
  
  RESULTS
  During in-hospital stay, no deaths, re-infarction nor recurrences of ischaemia requiring intervention were noted. The mean total duration of tirofiban administration was 21 hours. Thrombocytopenia was not observed in any patient. Bleeding complications occurred in 5 (17.9%) patients. Blood transfusion was required in three patients. The percentages of platelet inhibition measured at the pre-specified time-points were 95%, 94%, 91% and 87%, respectively. In 32% of patients an inhibition of platelet exceeding 95%, measured 10 minutes from the onset of tirofiban infusion, was not achieved. At the same time, platelet inhibition <90% was found in only 3 (11%) patients. Eight hours from the initiation of tirofiban, platelet inhibition <70% was found in 3 (11%) patients; of them, two had platelet inhibition <95% when measured 10 minutes from the onset of therapy with tirofiban.
  
  
  CONCLUSIONS
  1. Increased dosing of tirofiban resulted in an enhanced platelet inhibition. 2. Optimal platelet inhibition, especially during first minutes of drug administration, was not achieved in a substantial number of patients. 3. Increased IIb/IIIa inhibitor dosing resulted in a high partial and normal baseline coronary flow in an infarct-related artery. 4. Increased tirofiban dosing resulted in a relatively high bleeding complications rate.
authors.affiliation: Department of Invasive Cardiology, Medical Academy, Białystok, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Kralisz
authors.forename: Sławomir
authors.initials: S
authors.lastname: Dobrzycki
authors.forename: Konrad
authors.initials: K
authors.lastname: Nowak
authors.forename: Wacław
authors.initials: W
authors.lastname: Kochman
authors.forename: Hanna
authors.initials: H
authors.lastname: Gajewska-Bachórzewska
authors.forename: Kamil
authors.initials: K
authors.lastname: Gugała
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Mezyński
authors.forename: Przemysław
authors.initials: P
authors.lastname: Prokopczuk
authors.forename: Jerzy
authors.initials: J
authors.lastname: Zuk
authors.forename: Janusz
authors.initials: J
authors.lastname: Korecki
authors.forename: Bogusław
authors.initials: B
authors.lastname: Poniatowski
authors.forename: Włodzimierz
authors.initials: W
authors.lastname: Musiał
mesh_terms: D000328:Adult; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001792:Blood Platelets / Q000187:drug effects*; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D000077466:Tirofiban; D016896:Treatment Outcome; D014443:Tyrosine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D010975:Platelet Aggregation Inhibitors; D014443:Tyrosine; D000077466:Tirofiban