title: High rates of prasugrel and ticagrelor non-responder in patients treated with therapeutic hypothermia after cardiac arrest.
abstract: BACKGROUND
  After cardiac arrest due to acute coronary syndromes (ACS) therapeutic hypothermia (HT) is the standard care to reduce neurologic damage. Additionally, the concomitant medical treatment with aspirin and a P2Y12 receptor inhibitor like clopidogrel (Cl), prasugrel (Pr) or ticagrelor (Ti) is mandatory. The platelet inhibitory effect of these drugs under hypothermia remains unclear.
  
  
  METHODS
  164 patients with ACS were prospectively enrolled in this study. 84 patients were treated with HT, 80 patients were under normothermia (NT). All patients were treated with aspirin and one of the P2Y12 receptor inhibitors Cl, Pr or Ti. 24h after the initial loading dose the platelet reactivity index (PRI/VASP-index) was determined to achieve the platelet inhibitory effect.
  
  
  RESULTS
  In the HT-group the PRI/VASP-index was significantly higher compared to the NT-group (54.86%±25.1 vs. 28.98%±22.8; p<0.001). In patients under HT receiving Cl, the platelet inhibition was most markedly reduced (HT vs. NT: 66.39%±19.1 vs. 33.36%±22.1; p<0.001) compared to Pr (HT vs. NT: 37.6%±25.0 vs. 27.04%±25.5; p=0.143) and Ti (HT vs. NT: 41.5%±21.0 vs. 17.83%±14.5; p=0.009). The rate of non-responder defined as PRI/VASP-index>50% was increased in HT compared to NT (60.7% vs. 22.5%; p<0.001) with the highest rates in the group receiving Cl (CL: 82% vs. 26%, p<0.001; Pr: 32% vs. 23%; n.s.; Ti: 30% vs. 8%, n.s.).
  
  
  CONCLUSIONS
  The platelet inhibitory effect in patients treated with HT after cardiac arrest is significantly reduced. This effect was most marked with the use of Cl. The new P2Y12-inhibitors Pr and Ti improved platelet inhibition in HT, but could not completely prevent non-responsiveness.
authors.affiliation: Technische Universitaet Dresden, Heart Centre, University Hospital, Department of Internal Medicine and Cardiology, Germany. Electronic address: karim.ibrahim@mailbox.tu-dresden.de.
authors.forename: K
authors.initials: K
authors.lastname: Ibrahim
authors.affiliation: Technische Universitaet Dresden, Heart Centre, University Hospital, Department of Internal Medicine and Cardiology, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Christoph
authors.affiliation: Technische Universitaet Dresden, Heart Centre, University Hospital, Department of Internal Medicine and Cardiology, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schmeinck
authors.affiliation: Technische Universitaet Dresden, Heart Centre, University Hospital, Department of Internal Medicine and Cardiology, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Schmieder
authors.affiliation: Technische Universitaet Dresden, Heart Centre, University Hospital, Department of Internal Medicine and Cardiology, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Steiding
authors.affiliation: Technische Universitaet Dresden, Heart Centre, University Hospital, Department of Internal Medicine and Cardiology, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Schoener
authors.affiliation: Technische Universitaet Dresden, Heart Centre, University Hospital, Department of Internal Medicine and Cardiology, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Pfluecke
authors.affiliation: Technische Universitaet Dresden, Heart Centre, University Hospital, Department of Internal Medicine and Cardiology, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Quick
authors.affiliation: Technische Universitaet Dresden, Heart Centre, University Hospital, Department of Internal Medicine and Cardiology, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Mues
authors.affiliation: Technische Universitaet Dresden, Heart Centre, University Hospital, Department of Internal Medicine and Cardiology, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Jellinghaus
authors.affiliation: Technische Universitaet Dresden, Heart Centre, University Hospital, Department of Internal Medicine and Cardiology, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Wunderlich
authors.affiliation: Technische Universitaet Dresden, Heart Centre, University Hospital, Department of Internal Medicine and Cardiology, Germany.
authors.forename: R H
authors.initials: RH
authors.lastname: Strasser
authors.affiliation: Technische Universitaet Dresden, Heart Centre, University Hospital, Department of Internal Medicine and Cardiology, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Kolschmann
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077144:Clopidogrel; D005260:Female; D005434:Flow Cytometry; D006323:Heart Arrest / Q000628:therapy*; D006801:Humans; D007036:Hypothermia, Induced; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D000068799:Prasugrel Hydrochloride; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use*; D012307:Risk Factors; D013876:Thiophenes / Q000627:therapeutic use*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: Clopidogrel; Non-responder; Prasugrel; Therapeutic hypothermia; Ticagrelor