Dear Sir,
The platelet inhibitor clopidogrel is often part of dual anti-platelet therapy used for acute coronary syndromes. However, its effect depends on a sequential series of events, making it prone to failure [1]. The paper by Souckova et al. on the bioavailability of clopidogrel used during therapeutic hypothermia (TH) following cardiopulmonary resuscitation excellently illustrates this point, as only two of nine hypothermic patients showed adequate platelet inhibition. This was due to both delayed clopidogrel absorption and reduced bioavailability [2]. In the discussion of their findings, Souckova et al. could have lent further support for their conclusion by citing a previous larger study on clopidogrel efficacy during TH after cardiac arrest [3]. In this study, we observed that clopidogrel administered during TH was inefficacious in all 25 patients after 1 day of treatment. Moreover, only five of 16 subjects showed satisfactory clopidogrel platelet inhibition on day three. The clinical consequences are probably shown by Penela et al., who observed that stent thrombosis occurred in five out of 11 patients given percutaneous coronary intervention (16 stents were placed) and TH. This is an alarming rate compared to the 0.44 % reported for patients not treated with TH in the same period and hospital [4]. Preliminary results from a larger study presented by Ibrahim et al. at the ESC 2011 meeting also suggest a lack of clopidogrel effect during TH [5]. The conclusion from these studies is unequivocal: Clopidogrel should be replaced with an active, intravenously administrated drug in patients treated with TH.
References
Roden DM, Stein CM (2009) Clopidogrel and the concept of high-risk pharmacokinetics. Circulation 119:2127–2130
Souckova L, Opatrilova R, Suk P, Cundrle I Jr, Pavlik M, Zvonicek V, Hlinomaz O, Sramek V (2013) Impaired bioavailability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR). Eur J Clin Pharmacol 69:309–317
Bjelland TW, Hjertner O, Klepstad P, Kaisen K, Dale O, Haugen BO (2010) Antiplatelet effect of clopidogrel is reduced in patients treated with therapeutic hypothermia after cardiac arrest. Resuscitation 81:1627–1631
Penela D, Magaldi M, Fontanals J, Martin V, Regueiro A, Ortiz JT, Bosch X, Sabate M, Heras M (2013) Hypothermia in acute coronary syndrome: brain salvage versus stent thrombosis? J Am Coll Cardiol 61:686–687
Ibrahim K, Christoph M, Schmeinck S et al. (2011) Clopidogrel and prasugrel non-responder in therapeutic hypothermia after cardiac arrest. Abstract presented at the ESC 2011, Paris
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bjelland, T.W., Hjertner, Ø., Klepstad, P. et al. Clopidogrel does not work following cardiopulmonary resuscitation. Eur J Clin Pharmacol 69, 1727 (2013). https://doi.org/10.1007/s00228-013-1522-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-013-1522-8