Impaired bioavailability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR)

Součková, Lenka; Opatřilová, Radka; Suk, Pavel; Čundrle, Ivan; Pavlík, Martin; Zvoníček, Václav; Hlinomaz, Ota; Šrámek, Vladimír

doi:10.1007/s00228-012-1360-0

Cited by 57 publications

(40 citation statements)

References 50 publications

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“…29 It is also possible that hypothermia may delay gastric absorption and reduce the bioavailability of oral antiplatelet agents. 30 Penela et al described that among 16 patients presenting with acute coronary syndromes and cardiac arrest treated with PCI and hypothermia, 5 (31.2%) developed stent thrombosis within 30 days. 31 Conversely, in a consecutive series of 1334 patients with STEMI undergoing PCI, hypothermia in 75 cardiac arrest patients was not associated with an increased rate of stent thrombosis compared with control.…”

Section: Results Of the Current Study: Safetymentioning

confidence: 99%

Prospective, Multicenter, Randomized, Controlled Pilot Trial of Peritoneal Hypothermia in Patients With ST-Segment— Elevation Myocardial Infarction

Nichol

Strickland

Shavelle

et al. 2015

Circ: Cardiovascular Interventions

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Multiple methods to establish hypothermia have been explored. Hypothermia via external surface cooling or infusion of chilled intravenous fluid is limited by a slow rate of induction, temperature instability, and volume overload. Endovascular catheter-based cooling may induce hypothermia more quickly (4.8±2.1°C/h), 5,6,9,12 but still not fast enough toBackground-Systemic hypothermia may reduce infarct size if established before reperfusion. The large surface area of the bowel may facilitate rapid hypothermia. We therefore examined the feasibility, safety, and efficacy of hypothermia induced by an automated peritoneal lavage system in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Methods and Results-Patients with ST-segment-elevation myocardial infarction within 6 hours of symptom onset were randomized to peritoneal hypothermia before and for 3 hours after percutaneous coronary intervention versus control. The primary safety end point was the 30-day composite rate of death, reinfarction, ischemia-driven target vessel revascularization, major bleeding, sepsis, pneumonia, peritonitis, severe arrhythmia, or renal failure. The primary efficacy end point was infarct size assessed by cardiac MRI on day 3 to 5. Fifty-four patients were randomized at 7 centers to hypothermia (n=28) versus control (n=26

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Section: Results Of the Current Study: Safetymentioning

confidence: 99%

Prospective, Multicenter, Randomized, Controlled Pilot Trial of Peritoneal Hypothermia in Patients With ST-Segment— Elevation Myocardial Infarction

Nichol

Strickland

Shavelle

et al. 2015

Circ: Cardiovascular Interventions

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“…Bjelland et al showed that after therapeutic hypothermia the effect of clopidogrel is non-existent in the first day of treatment and during the third day the recovery in partial [63]. Also there is evidence that bioavailability of clopidogrel is reduced in hemodynamic unstable patients after successful cardio-pulmonary resuscitation [64].…”

Section: Mechanisms For Anti-platelet Drugs Resistance In Critically mentioning

confidence: 99%

Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

Mărginean

Bănescu

Scridon

et al. 2016

The Journal of Critical Care Medicine

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It is well known that critically ill patients require special attention and additional consideration during their treatment and management. The multiple systems and organ dysfunctions, typical of the critical patient, often results in different patterns of enteral absorption in these patients. Anti-platelet drugs are the cornerstone in treating patients with coronary and cerebrovascular disease. Dual anti-platelet therapy with aspirin and clopidogrel is the treatment of choice in patients undergoing elective percutaneous coronary interventions and is still widely used in patients with acute coronary syndromes. However, despite the use of dual anti-platelet therapy, some patients continue to experience cardiovascular ischemic events. Recurrence of ischemic events is partly attributed to the fact that some patients have poor inhibition of platelet reactivity despite treatment. These patients are considered low-or nonresponders to therapy. The underlying mechanisms leading to resistance are not yet fully elucidated and are probably multifactorial, cellular, genetic and clinical factors being implicated. Several methods have been developed to asses platelet function and can be used to identify patients with persistent platelet reactivity, which have an increased risk of thrombosis. In this paper, the concept of anti-platelet therapy resistance, the underlying mechanisms and the methods used to identify patients with low responsiveness to anti-platelet therapy will be highlighted with a focus on aspirin and clopidogrel therapy and addressing especially critically ill patients.

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“…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].…”

mentioning

confidence: 93%

Clopidogrel does not work following cardiopulmonary resuscitation

Bjelland

Hjertner

Klepstad

et al. 2013

Eur J Clin Pharmacol

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Dear Sir, The platelet inhibitor clopidogrel is often part of dual antiplatelet 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.

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Impaired bioavailability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR)

Abstract: The bioavailability of clopidogrel in critically ill patients after cardiopulmonary resuscitation is significantly impaired compared with stable patients. Therefore, other drugs, preferentially administered intravenously, should be considered.

Cited by 57 publications

References 50 publications

Prospective, Multicenter, Randomized, Controlled Pilot Trial of Peritoneal Hypothermia in Patients With ST-Segment— Elevation Myocardial Infarction

Prospective, Multicenter, Randomized, Controlled Pilot Trial of Peritoneal Hypothermia in Patients With ST-Segment— Elevation Myocardial Infarction

Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

Clopidogrel does not work following cardiopulmonary resuscitation

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