title: Impact of mild hypothermia on platelet responsiveness to aspirin and clopidogrel: an in vitro pharmacodynamic investigation.
abstract: The combination of percutaneous coronary intervention (PCI) and therapeutic hypothermia in comatose patients after cardiac arrest due to an acute coronary syndrome has been reported to be safe and effective. However, recent investigations suggest that hypothermia may be associated with impaired response to clopidogrel and greater risk of thrombotic complications after PCI. This investigation aimed to evaluate the effect of hypothermia on the pharmacodynamic response of aspirin and clopidogrel in patients (n = 20) with ST elevation myocardial infarction undergoing primary PCI. Higher platelet reactivity (ADP stimulus) was observed in samples incubated at 33 °C compared with those at 37 °C (multiple electrode aggregometry, 235.2 ± 31.4 AU×min vs. 181.9 ± 30.2 AU×min, p < 0.001; VerifyNow P2Y12, 172.9 ± 20.3 PRU vs. 151.0 ± 19.3 PRU, p = 0.004). Numerically greater rates of clopidogrel poor responsiveness were also observed at 33 °C. No differences were seen in aspirin responsiveness. In conclusion, mild hypothermia was associated with reduced clopidogrel-mediated platelet inhibition with no impact on aspirin effects.
  
  
  CONCLUSIONS
  Mild therapeutic hypothermia is associated with impaired response to clopidogrel therapy, which might contribute to increase the risk of thrombotic events in ACS comatose patients undergoing PCI.
authors.affiliation: Heart Diseases Institute, Bellvitge University Hospital-IDIBELL, University of Barcelona, c/Feixa Llarga s/n. CP 08907 L'Hospitalet de Llobregat, Barcelona, Spain, jlferreiro@bellvitgehospital.cat.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Ferreiro
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Sánchez-Salado
authors.forename: Montserrat
authors.initials: M
authors.lastname: Gracida
authors.forename: Ana Lucrecia
authors.initials: AL
authors.lastname: Marcano
authors.forename: Gerard
authors.initials: G
authors.lastname: Roura
authors.forename: Albert
authors.initials: A
authors.lastname: Ariza
authors.forename: Josep
authors.initials: J
authors.lastname: Gómez-Lara
authors.forename: Victoria
authors.initials: V
authors.lastname: Lorente
authors.forename: Rafael
authors.initials: R
authors.lastname: Romaguera
authors.forename: Sílvia
authors.initials: S
authors.lastname: Homs
authors.forename: Guillermo
authors.initials: G
authors.lastname: Sánchez-Elvira
authors.forename: Luis
authors.initials: L
authors.lastname: Teruel
authors.forename: Kristian
authors.initials: K
authors.lastname: Rivera
authors.forename: Silvia Gabriela
authors.initials: SG
authors.lastname: Sosa
authors.forename: Joan Antoni
authors.initials: JA
authors.lastname: Gómez-Hospital
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.forename: Angel
authors.initials: A
authors.lastname: Cequier
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000077144:Clopidogrel; D003328:Coronary Thrombosis / Q000209:etiology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011446:Prospective Studies; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects; D012307:Risk Factors; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin