Mild hypothermia does not attenuate platelet aggregation and may even increase ADP-stimulated platelet aggregation after clopidogrel treatment

Högberg, Carl; Erlinge, David; Braun, Öscar

doi:10.1186/1477-9560-7-2

Cited by 45 publications

(57 citation statements)

References 21 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Of note, an excess of stent thrombosis has never been reported in any of the previous endovascular cooling studies [9][10][11][12] . However, core temperature in our study was ≥1.1°C lower and this might have increased platelet aggregation 16,17 . Furthermore, resorption and metabolism of clopidogrel, used in 24% of our hypothermia group, is slower in cooled and sedated patients 18 .…”

Section: Cool Ami Eu Pilot Trialmentioning

confidence: 68%

COOL AMI EU pilot trial: a multicentre, prospective, randomised controlled trial to assess cooling as an adjunctive therapy to percutaneous intervention in patients with acute myocardial infarction

Noč¹,

Erlinge²,

Nešković³

et al. 2017

EuroIntervention

Self Cite

View full text Add to dashboard Cite

Aims: We aimed to investigate the rapid induction of therapeutic hypothermia using the ZOLL Proteus Intravascular Temperature Management System in patients with anterior ST-elevation myocardial infarction (STEMI) without cardiac arrest. Methods and results:A total of 50 patients were randomised; 22 patients (88%; 95% confidence interval [CI]: 69-97%) in the hypothermia group and 23 patients (92%; 95% CI: 74-99) in the control group completed cardiac magnetic resonance imaging at four to six days and 30-day follow-up. Intravascular temperature at coronary guidewire crossing after 20.5 minutes of endovascular cooling decreased to 33.6°C (range 31.9-35.5°C). There was a 17-minute (95% CI: 4.6-29.8 min) cooling-related delay to reperfusion. In "per protocol" analysis, median infarct size/left ventricular mass was 16.7% in the hypothermia group versus 23.8% in the control group (absolute reduction 7.1%, relative reduction 30%; p=0.31) and median left ventricular ejection fraction (LVEF) was 42% in the hypothermia group and 40% in the control group (absolute reduction 2.4%, relative reduction 6%; p=0.36). Except for self-terminating paroxysmal atrial fibrillation (32% versus 8%; p=0.074), there was no excess of adverse events in the hypothermia group.Conclusions: We rapidly and safely cooled patients with anterior STEMI to 33.6°C at the time of coronary guidewire crossing. This is ≥1.1°C lower than in previous cooling studies. Except for self-terminating atrial fibrillation, there was no excess of adverse events and no clinically important cooling-related delay to reperfusion. A statistically non-significant numerical 7.1% absolute and 30% relative reduction in infarct size warrants a pivotal trial powered for efficacy. ClinicalTrials.

show abstract

Section: Cool Ami Eu Pilot Trialmentioning

confidence: 68%

COOL AMI EU pilot trial: a multicentre, prospective, randomised controlled trial to assess cooling as an adjunctive therapy to percutaneous intervention in patients with acute myocardial infarction

Noč¹,

Erlinge²,

Nešković³

et al. 2017

EuroIntervention

Self Cite

View full text Add to dashboard Cite

show abstract

“…A number of recent studies also indicate that, contrary to the widely accepted theory about hypocoagulation during hypothermia, platelet activation may increase under conditions of MTH, which may also contribute to the reduced inhibitory effects of antiplatelet drugs [18][19][20]. Another very important factor that may apply to this subgroup of patients is reduced ejection fraction and hemodynamic instability or cardiogenic shock [13,21].…”

Section: Discussionmentioning

confidence: 86%

Antiplatelet efficacy of P2Y12 inhibitors (prasugrel, ticagrelor, clopidogrel) in patients treated with mild therapeutic hypothermia after cardiac arrest due to acute myocardial infarction

Bednář

Kroupa

Ondrakova

et al. 2015

J Thromb Thrombolysis

View full text Add to dashboard Cite

Survivors after cardiac arrest (CA) due to AMI undergo PCI and then receive dual antiplatelet therapy. Mild therapeutic hypothermia (MTH) is recommended for unconscious patients after CA to improve neurological outcomes. MTH can attenuate the effectiveness of P2Y12 inhibitors by reducing gastrointestinal absorption and metabolic activation. The combined effect of these conditions on the efficacy of P2Y12 inhibitors is unknown. We compared the antiplatelet efficacies of new P2Y12 inhibitors in AMI patients after CA treated with MTH. Forty patients after CA for AMI treated with MTH and received one P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) were enrolled in a prospective observational single-center study. Platelet inhibition was measured by VASP (PRI) on days 1, 2, and 3 after drug administration. In-hospital clinical data and 1-year survival data were obtained. The proportion of patients with ineffective platelet inhibition (PRI > 50 %, high on-treatment platelet reactivity) for clopidogrel, prasugrel, and ticagrelor was 77 vs. 19 vs. 1 % on day 1; 77 vs. 17 vs. 0 % on day 2; and 85 vs. 6 vs. 0 % on day 3 (P < 0.001). The platelet inhibition was significantly worse in clopidogrel group than in prasugrel or ticagrelor group. Prasugrel and ticagrelor are very effective for platelet inhibition in patients treated with MTH after CA due to AMI, but clopidogrel is not. Using prasugrel or ticagrelor seems to be a more suitable option in this high-risk group of acute patients.

show abstract

“…However, several studies in the literature report the influence of hypothermia on pharmacodynamics, pharmacokinetics, and drug effects. [15][16][17] Whether cooling modifies the effect of ascorbic acid on myocardial function and outcomes in cardiac arrest survivors remains unclear. Therefore, we hypothesized that ascorbic acid administration after ROSC will improve myocardial function and outcomes.…”

mentioning

confidence: 99%

Combination of Intravenous Ascorbic Acid Administration and Hypothermia After Resuscitation Improves Myocardial Function and Survival in a Ventricular Fibrillation Cardiac Arrest Model in the Rat

Tsai

Huang

Tsai

et al. 2014

Academic Emergency Medicine

View full text Add to dashboard Cite

Objectives: Intravenous (IV) administration of ascorbic acid during cardiopulmonary resuscitation (CPR) was reported to facilitate defibrillation and improves survival in ventricular fibrillation (VF) cardiac arrest. We investigated whether IV administration of ascorbic acid after return of spontaneous circulation (ROSC) can improve outcomes in VF cardiac arrest in a rat model and its interaction with therapeutic hypothermia.Methods: Ventricular fibrillation-induced cardiac arrest followed by CPR and defibrillation was performed in male Wistar rats. After ROSC, the animals were equally randomized to the normothermia (NormoT), hypothermia (HypoT), ascorbic acid (AA+NormoT), and ascorbic acid plus hypothermia (AA+HypoT) groups. The AA+NormoT and AA+HypoT groups received IV ascorbic acid (100 mg/kg). In the HypoT and AA+HypoT groups, therapeutic hypothermia was maintained at 32°C for 2 hours.Results: There were 12 rats in each group. Within 4 hours after ROSC, the HypoT, AA+NormoT, and AA+HypoT groups had significantly lower myocardial lipid peroxidation than the NormoT group. Within 4 hours following ROSC, the AA+NormoT group had a significantly better systolic function (dp/dt 40 ) than the NormoT group (6887.9 mm Hg/sec, SD AE 1049.7 mm Hg/sec vs. 5953.6 mm Hg/sec, SD AE 1161.9 mm Hg/sec; p < 0.05). The AA+HypoT group also showed a significantly better diastolic function (-dp/dt max ) than the HypoT group (dp/dt 40 : 8524.8, SD AE 1166.7 mm Hg/sec vs. 7399.8 mm Hg/sec, SD AE 1114.5 mmHg/sec; dp/dt max : -8183.4 mm Hg/sec, SD AE 1359.0 mm Hg/sec vs. -6573.7 mm Hg/sec, SD AE 1110.9 mm Hg/sec; p < 0.05) at the fourth hour following ROSC. Also at 4 hours, there was less myocytolysis in the HypoT, AA+NormoT, and AA+HypoT groups than the NormoT group. The HypoT, AA+NormoT, and AA+HypoT groups had significantly better survival rates and neurologic outcomes than the NormoT group. Compared with only five surviving animals in the NormoT group, there were nine, eight, and 10 in the HypoT, AA+NormoT, and AA+HypoT groups, respectively, with good neurologic outcomes at 72 hours.Conclusions: Intravenous ascorbic acid administration after ROSC in normothermia may mitigate myocardial damage and improve systolic function, survival rate, and neurologic outcomes in VF cardiac arrest of rat. Combination of ascorbic acid and hypothermia showed an additive effect in improving both systolic and diastolic functions after ROSC.ACADEMIC EMERGENCY MEDICINE 2014; 21:257-265

show abstract

Mild hypothermia does not attenuate platelet aggregation and may even increase ADP-stimulated platelet aggregation after clopidogrel treatment

Cited by 45 publications

References 21 publications

COOL AMI EU pilot trial: a multicentre, prospective, randomised controlled trial to assess cooling as an adjunctive therapy to percutaneous intervention in patients with acute myocardial infarction

COOL AMI EU pilot trial: a multicentre, prospective, randomised controlled trial to assess cooling as an adjunctive therapy to percutaneous intervention in patients with acute myocardial infarction

Antiplatelet efficacy of P2Y12 inhibitors (prasugrel, ticagrelor, clopidogrel) in patients treated with mild therapeutic hypothermia after cardiac arrest due to acute myocardial infarction

Combination of Intravenous Ascorbic Acid Administration and Hypothermia After Resuscitation Improves Myocardial Function and Survival in a Ventricular Fibrillation Cardiac Arrest Model in the Rat

Contact Info

Product

Resources

About