Impact of mild hypothermia on platelet responsiveness to aspirin and clopidogrel: an in vitro pharmacodynamic investigation.

ABSTRACT

UNLABELLED 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.