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Impact of Mild Hypothermia on Platelet Responsiveness to Aspirin and Clopidogrel: an In Vitro Pharmacodynamic Investigation

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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.

Clinical relevance: 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.

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Conflict of Interest

José Luis Ferreiro (corresponding author) reports (a) honoraria for lectures from Eli Lilly Co., Daiichi Sankyo, Inc., and Astra Zeneca and (b) consulting fees from Astra Zeneca and Eli Lilly Co. Dominick J. Angiolillo received payment as an individual for (a) consulting fee or honorarium from Bristol Myers Squibb, Sanofi-Aventis, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, Merck, Evolva, Abbott Vascular, and PLx Pharma and (b) participation in review activities from Johnson & Johnson, St. Jude, and Sunovion. Institutional payments for grants from Bristol Myers Squibb, Sanofi-Aventis, Glaxo Smith Kline, Otsuka, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, and Evolva and has other financial relationships with Esther and King Biomedical Research Grant.

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  1. Heart Diseases Institute, Bellvitge University Hospital—IDIBELL, University of Barcelona, c/Feixa Llarga s/n. CP 08907 L’Hospitalet de Llobregat, Barcelona, Spain

    José Luis Ferreiro, José Carlos Sánchez-Salado, Montserrat Gracida, Ana Lucrecia Marcano, Gerard Roura, Albert Ariza, Josep Gómez-Lara, Victoria Lorente, Rafael Romaguera, Sílvia Homs, Guillermo Sánchez-Elvira, Luis Teruel, Kristian Rivera, Silvia Gabriela Sosa, Joan Antoni Gómez-Hospital & Ángel Cequier

  2. University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA

    Dominick J. Angiolillo

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Correspondence to José Luis Ferreiro.

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Associate Editor Emanuele Barbato oversaw the review of this article

José Luis Ferreiro and José Carlos Sánchez-Salado have contributed equally as first authors to this manuscript.

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Ferreiro, J.L., Sánchez-Salado, J.C., Gracida, M. et al. Impact of Mild Hypothermia on Platelet Responsiveness to Aspirin and Clopidogrel: an In Vitro Pharmacodynamic Investigation. J. of Cardiovasc. Trans. Res. 7, 39–46 (2014). https://doi.org/10.1007/s12265-013-9533-5

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