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

Ferreiro, José Luis; Sánchez‐Salado, José Carlos; Gracida, Montserrat; Marcano, Ana Lucrecia; Roura, Gerard; Ariza, Albert; Gómez-Lara, Josep; Lorente, Victòria; Romaguera, Rafael; Homs, Sílvia; Sánchez-Elvira, Guillermo; Teruel, Luís; Rivera, Kristian; Sosa, Silvia Gabriela; Gómez‐Hospital, Joan Antoni; Angiolillo, Dominick J.; Cequier, Ángel

doi:10.1007/s12265-013-9533-5

Cited by 18 publications

(15 citation statements)

References 46 publications

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“…An in vitro study by Ferreiro et al (2014) investigated the effect of hypothermia on the pharmacodynamics of clopidogrel and aspirin. In this study, blood samples were obtained from 20 patients who underwent percutaneous coronary intervention and received loading doses of aspirin and clopidogrel.…”

Section: Effect Of Ttm On Pharmacodynamicsmentioning

confidence: 99%

Effect of Hypothermia and Targeted Temperature Management on Drug Disposition and Response Following Cardiac Arrest: A Comprehensive Review of Preclinical and Clinical Investigations

Anderson

Poloyac

Kochanek

et al. 2016

Therapeutic Hypothermia and Temperature Management

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Targeted temperature management (TTM) has been shown to reduce mortality and improve neurological outcomes in out-of-hospital cardiac arrest (CA) patients and in neonates with hypoxic-ischemic encephalopathy (HIE). TTM has also been associated with adverse drug events in the critically ill patient due to its effect on drug pharmacokinetics (PKs) and pharmacodynamics (PDs). We aim to evaluate the current literature on the effect of TTM on drug PKs and PDs following CA. MEDLINE/PubMed databases were searched for publications, which include the MeSH terms hypothermia, drug metabolism, drug transport, P450, critical care, cardiac arrest, hypoxic-ischemic encephalopathy, pharmacokinetics, and pharmacodynamics between July 2006 and October 2015. Twenty-three studies were included in this review. The studies demonstrate that hypothermia impacts PK parameters and increases concentrations of cytochrome-P450-metabolized drugs in the cooling and rewarming phase. Furthermore, the current data demonstrate a combined effect of CA and hypothermia on drug PK. Importantly, these effects can last greater than 4-5 days post-treatment. Limited evidence suggests hypothermia-mediated changes in the Phase II metabolism and the Phase III transport of drugs. Hypothermia also has been shown to potentially decrease the effect of specific drugs at the receptor level. Therapeutic hypothermia, as commonly deployed/applied during TTM, alters PK, and elevates concentrations of several commonly used medications. Hypothermia-mediated effects are an important factor when dosing and monitoring patients undergoing TTM treatment.

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Section: Effect Of Ttm On Pharmacodynamicsmentioning

confidence: 99%

Effect of Hypothermia and Targeted Temperature Management on Drug Disposition and Response Following Cardiac Arrest: A Comprehensive Review of Preclinical and Clinical Investigations

Anderson

Poloyac

Kochanek

et al. 2016

Therapeutic Hypothermia and Temperature Management

View full text Add to dashboard Cite

show abstract

“…The vast majority of studies were conducted under moderate TH (33°C) that lasted 24 hours, whereas mild (36°C) TH or different duration of TH was investigated to a lesser extent. Although some discrepancies exist among the published results, most studies demonstrate that moderate TH reduces P2Y 12 ‐mediated platelet inhibitory effect …”

Section: Th and P2y12 Inhibitorsmentioning

confidence: 96%

“…As mentioned above, Ferreiro et al . evaluated the effect of hypothermia on the pharmacodynamic response to DAPT (combination of ASA and clopidogrel).…”

Section: Th and P2y12 Inhibitorsmentioning

confidence: 99%

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Effectiveness of Antiplatelet Drugs Under Therapeutic Hypothermia: A Comprehensive Review

Eyileten

Pordzik

Siller-Matula

et al. 2019

Clin Pharma and Therapeutics

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Out‐of‐hospital cardiac arrest is among the most frequent causes of death worldwide. Immediate intervention, as well as dual antiplatelet therapy consisting of acetylsalicylic acid and a P2Y12 inhibitor is often recommended. In line with the growing number of reports on cardiac arrest treatment, therapeutic hypothermia (TH) has been proposed for unconscious patients to improve neurological outcomes. Nevertheless, studies report controversial and often discrepant results on the effect of hypothermia on blood coagulability and platelet reactivity. In this review, we summarize the knowledge on platelet function under diverse hypothermic conditions. Additionally, we review the current literature on the effect of systemic hypothermia on pharmacokinetic and pharmacodynamic properties of antiplatelet agents. It has been shown that TH can alter the effectiveness of antiplatelet agents, including P2Y12 inhibitors, through multiple mechanisms, hence, special attention should be paid while implementing antiplatelet therapy in patients under TH conditions.

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“…The heterogeneity in response to current antiplatelet regimens with related clinical implications has been described in the following clinical settings [61][62][63][64]: (a) an impaired response to clopidogrel has been observed under conditions mimicking the hypothermic state of the comatose patients after ACS undergoing percutaneous coronary interventions (PCI), [62] (b) difficult therapeutic management with related increased bleeding risk in patients under chronic anticoagulation treated with PCI [60], (c) challenges of bridging antiplatelet therapy in patients requiring cardiac and noncardiac surgery [64], and (d) the gender differences in antiplatelet treatments and responses [65]. Future areas of investigations have been proposed in novel antiplatelet agents able to potently and safely inhibit platelet reactivity [66,67].…”

Section: Antiplatelet Therapy Optimization: From Inflammation To Acutmentioning

confidence: 99%

Review and Updates in Regenerative and Personalized Medicine, Preclinical Animal Models, and Clinical Care in Cardiovascular Medicine

Barbato

Barton

Bartúnek

et al. 2015

J. of Cardiovasc. Trans. Res.

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The goal of this paper is to provide an updated review for scientists and clinicians on the major areas in cardiovascular medicine published in the Journal. Leading topics in regenerative and personalized medicine are presented along with a critical overview of the field. New standards in large preclinical animal models of pulmonary hypertension and left bundle branch block are highlighted. Finally, clinical care in the areas of atherosclerosis, the aortic valve, platelet biology, and myocarditis is discussed as well as autonomic modulation therapies

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

Abstract: 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.

Cited by 18 publications

References 46 publications

Effect of Hypothermia and Targeted Temperature Management on Drug Disposition and Response Following Cardiac Arrest: A Comprehensive Review of Preclinical and Clinical Investigations

Effect of Hypothermia and Targeted Temperature Management on Drug Disposition and Response Following Cardiac Arrest: A Comprehensive Review of Preclinical and Clinical Investigations

Effectiveness of Antiplatelet Drugs Under Therapeutic Hypothermia: A Comprehensive Review

Review and Updates in Regenerative and Personalized Medicine, Preclinical Animal Models, and Clinical Care in Cardiovascular Medicine

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