Clopidogrel pharmacokinetics and pharmacodynamics in out-of-hospital cardiac arrest patients with acute coronary syndrome undergoing target temperature management

  • J. K
  • E. W
  • H. S
 et al. 
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Abstract

Background: Target temperature management (TTM) after cardiac arrest (CA) improves outcome in patients with acute coronary syndrome (ACS). Previous data point to an interaction between hypothermia and drug metabolism, potentially impacting on platelet function in patients on antiplatelet therapy. Purpose: To compare clopidogrel metabolism and platelet function in clopidogrel naïve ACS patients treated with TTM (33 °C, n = 15) and in ACS patients (troponin positive) without TTM (n = 18). Methods: Platelet function was measured by multiple electrode platelet aggregometry (MEA), light transmittance aggregometry (LTA) and VASP analysis before and after administration of a 600 mg clopidogrel loading dose. Plasma levels of clopidogrel and its metabolites were measured. All patients were screened for CYP2C19*2 polymorphism and scheduled for PCI. TTM was carried out for 24 h at a target temperature of 33 °C using a computer feedback surface cooling device in cardiac arrest patients. Results: Plasma concentration of clopidogrel and metabolites was lower in the TTM group after 2 and 4 h, respectively (all p < 0.005 vs. controls), and platelet function tests revealed an attenuated response to clopidogrel with respect to baseline platelet activity in the TTM group. This was significant for MEA, LTA and VASP analysis (all p < 0.05). Moreover, there was no significant difference in genotype and platelet function determined ex vivo at 33 or 37 °C, respectively. Conclusion: Inhibition of platelet function is significantly lessened in TTM at 33 °C, likely due to reduced clopidogrel absorption. Patients with TTM might thus have a higher risk for further cardiovascular events despite antiplatelet therapy with clopidogrel.

Author-supplied keywords

  • acute coronary syndrome
  • aged
  • analytic method
  • article
  • blood analysis
  • blood clotting parameters
  • clinical article
  • clopidogrel
  • controlled study
  • cytochrome P450 2C19
  • drug blood level
  • drug metabolism
  • ex vivo study
  • feedback system
  • female
  • genetic polymorphism
  • genotype
  • human
  • light transmittance aggregometry
  • loading drug dose
  • male
  • multiple electrode platelet aggregometry
  • out of hospital cardiac arrest
  • pharmacodynamics
  • priority journal
  • target temperature management
  • temperature dependence
  • thermoregulation
  • thrombocyte function
  • treatment response
  • troponin

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Authors

  • Kaufmann J.

  • Wellnhofer E.

  • Stockmann H.

  • Graf K.

  • Fleck E.

  • Schroeder T.

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