title: Platelet inhibition with prasugrel in patients with acute myocardial infarction undergoing therapeutic hypothermia after cardiopulmonary resuscitation.
abstract: Acute myocardial infarction (AMI) is the leading cause for out-of-hospital cardiac arrest. Therapeutic hypothermia improves neurological outcome in combination with early revascularisation, but seems to affect clopidogrel responsiveness. The more potent thienopyridine prasugrel has not yet been sufficiently evaluated during therapeutic hypothermia. We investigated 23 consecutive AMI patients (61 ± 11 years) following out-of-hospital resuscitation undergoing revascularisation and therapeutic hypothermia. Prasugrel efficacy was assessed by the platelet-reactivity-index (PRI) before and 2, 4, 6, 12, 24, 48, and 72 hours (h) following a loading dose of 60 mg via a gastric tube. Mean PRI (± SD) was 70 ± 12 % prior to loading and 60 ± 16 % (2 h, ns), 52 ± 21 % (4 h, p< 0.01), 42 ± 26 % (6 h, p< 0.01), 37 ± 21 % (12 h, p< 0.01), 27 ± 23 % (24 h, p< 0.01), 18 ± 14 % (48 h, p< 0.01), and 13 ± 10 % (72 h, p< 0.01) after loading. Sufficient platelet inhibition occurred later compared to stable AMI patients (6 h vs 2 h); however, high on-treatment platelet reactivity significantly decreased over time and was non-existent after 72 h (PRI> 50 %: 2 h: 72 %, 4 h: 52 %, 6 h: 43 %, 12 h: 29 %, 24 h: 17 %, 48 h: 5 %, 72 h: 0 %). There was no relation between 30-day mortality rate (26 %) and PRI values. Prasugrel significantly reduced platelet reactivity even during vasopressor use, analgosedation and therapeutic hypothermia. Despite a significant delay compared to stable AMI patients, sufficient platelet inhibition was reached in 83 % of patients within 24 h. Therefore, prasugrel administration via gastric tube might be a useful therapeutic strategy in these patients at high risk, providing potent and effective P2Y12 inhibition.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Flierl
authors.forename: Philipp
authors.initials: P
authors.lastname: Röntgen
authors.forename: Florian
authors.initials: F
authors.lastname: Zauner
authors.forename: Jörn
authors.initials: J
authors.lastname: Tongers
authors.forename: Dominik
authors.initials: D
authors.lastname: Berliner
authors.forename: Johann
authors.initials: J
authors.lastname: Bauersachs
authors.affiliation: Prof. Dr. Andreas Schäfer, Medizinische Hochschule Hannover, Klinik für Kardiologie und Angiologie, Carl Neuberg Straße 1, 30625 Hannover, Germany, Tel: +49 511 532 5240; Fax: +49 511 532 8244, E-mail: Schaefer.andreas@mh-hannover.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schäfer
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects; D016887:Cardiopulmonary Resuscitation; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride / Q000627:therapeutic use*; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use; D000072657:ST Elevation Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000068799:Prasugrel Hydrochloride
keywords: Therapeutic hypothermia; acute coronary syndrome; cardiac arrest; prasugrel