title: High Platelet Reactivity in Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: Randomised Controlled Trial Comparing Prasugrel and Clopidogrel.
abstract: BACKGROUND
  Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited.
  
  
  OBJECTIVE
  To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS).
  
  
  METHODS
  Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. "poor responders" were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors.
  
  
  RESULTS
  At 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively.
  
  
  CONCLUSIONS
  Routine platelet function testing identifies patients with high residual platelet reactivity ("poor responders") on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01339026.
authors: Klinikum der Eberhard-Karls-Universität Tübingen, Abteilung für Kardiologie und Kreislauferkrankungen, Tübingen, Germany.
authors: Tobias
authors: T
authors: Geisler
authors: Clinical Trials & Evaluation Unit, Royal Brompton Hospital, London, United Kingdom.
authors: Jean
authors: J
authors: Booth
authors: Klinikum der Eberhard-Karls-Universität Tübingen, Abteilung für Kardiologie und Kreislauferkrankungen, Tübingen, Germany.
authors: Elli
authors: E
authors: Tavlaki
authors: Klinikum der Eberhard-Karls-Universität Tübingen, Abteilung für Kardiologie und Kreislauferkrankungen, Tübingen, Germany.
authors: Athanasios
authors: A
authors: Karathanos
authors: Klinikum der Eberhard-Karls-Universität Tübingen, Abteilung für Kardiologie und Kreislauferkrankungen, Tübingen, Germany.
authors: Karin
authors: K
authors: Müller
authors: Klinikum der Eberhard-Karls-Universität Tübingen, Abteilung für Kardiologie und Kreislauferkrankungen, Tübingen, Germany.
authors: Michal
authors: M
authors: Droppa
authors: Klinikum der Eberhard-Karls-Universität Tübingen, Abteilung für Kardiologie und Kreislauferkrankungen, Tübingen, Germany.
authors: Meinrad
authors: M
authors: Gawaz
authors: Clinical Trials & Evaluation Unit, Royal Brompton Hospital, London, United Kingdom.
authors: Monica
authors: M
authors: Yanez-Lopez
authors: Dept. Haematology, Royal Brompton&Harefield NHS Foundation Trust, London, United Kingdom.
authors: Simon J
authors: SJ
authors: Davidson
authors: Liverpool Heart and Chest Hospital, Liverpool, United Kingdom.
authors: Rod H
authors: RH
authors: Stables
authors: Clinical Trials & Evaluation Unit, Royal Brompton Hospital, London, United Kingdom.
authors: Winston
authors: W
authors: Banya
authors: Freeman Hospital and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors: Azfar
authors: A
authors: Zaman
authors: Norfolk and Norwich University Hospitals NHS Foundation Trust and Norwich Medical School, University of East Anglia, Norfolk, United Kingdom.
authors: Marcus
authors: M
authors: Flather
authors: Harefield Hospital, Royal Brompton & Harefield NHS Foundation Trust, London, United Kingdom.
authors: Miles
authors: M
authors: Dalby
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000628:therapy*; D000244:Adenosine Diphosphate / Q000378:metabolism / Q000494:pharmacology; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects*; D000077144:Clopidogrel; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000068799:Prasugrel Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use*; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D012307:Risk Factors; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine