Platelet inhibition with prasugrel in patients with acute myocardial infarction undergoing therapeutic hypothermia after cardiopulmonary resuscitation

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 com- pared 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.