Subscribe to RSS
DOI: 10.1160/TH15-07-0599
Platelet inhibition with prasugrel in patients with acute myocardial infarction undergoing therapeutic hypothermia after cardiopulmonary resuscitation
Publication History
Received:
29 July 2015
Accepted after major revision:
22 January 2015
Publication Date:
06 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/201605/lookinside/thumbnails/10.1160-th15-07-0599-1.jpg)
Summary
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.
* UF and PR contributed equally to the manuscript.
-
References
- 1 Dumas F, Cariou A, Manzo-Silberman S. et al. Immediate percutaneous coronary intervention is associated with better survival after out-of-hospital cardiac arrest: insights from the PROCAT (Parisian Region Out of hospital Cardiac ArresT) registry. Circ Cardiovasc Interv 2010; 3: 200-207.
- 2 Spaulding CM, Joly LM, Rosenberg A. et al. Immediate coronary angiography in survivors of out-of-hospital cardiac arrest. N Engl J Med 1997; 336: 1629-1633.
- 3 Arntz HR, Bossaert LL, Danchin N. et al. European Resuscitation Council Guidelines for Resuscitation 2010 Section 5. Initial management of acute coronary syndromes. Resuscitation 2010; 81: 1353-1363.
- 4 Task Force on the management of STseamiotESoC. Steg PG, James SK. et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33: 2569-2619.
- 5 Joffre J, Varenne O, Bougouin W. et al. Stent thrombosis: an increased adverse event after angioplasty following resuscitated cardiac arrest. Resuscitation. 2014 Epub ahead of print.
- 6 O’Connor RE, Brady W, Brooks SC. et al. Part 10: acute coronary syndromes: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010; 122 (18) (Suppl. 03) S787-S817.
- 7 Bernard SA, Gray TW, Buist MD. et al. Treatment of comatose survivors of outof- hospital cardiac arrest with induced hypothermia. N Engl J Med 2002; 346: 557-563.
- 8 Hypothermia after Cardiac Arrest Study G. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002; 346: 549-556.
- 9 Bjelland TW, Hjertner ø, Klepstad P. et al. Antiplatelet effect of clopidogrel is reduced in patients treated with therapeutic hypothermia after cardiac arrest. Resuscitation 2010; 81: 1627-1631.
- 10 Högberg C, Erlinge D, Braun OO. Mild hypothermia does not attenuate platelet aggregation and may even increase ADP-stimulated platelet aggregation after clopidogrel treatment. Thrombosis J 2009; 7: 2.
- 11 Montalescot G, Wiviott SD, Braunwald E. et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet 2009; 373: 723-731.
- 12 Steg PG, James S, Harrington RA. et al. Ticagrelor versus clopidogrel in patients with ST-elevation acute coronary syndromes intended for reperfusion with primary percutaneous coronary intervention: A Platelet Inhibition and Patient Outcomes (PLATO) trial subgroup analysis. Circulation 2010; 122: 2131-2141.
- 13 Osmancik P, Jirmar R, Hulikova K. et al. A comparison of the VASP index between patients with hemodynamically complicated and uncomplicated acute myocardial infarction. Catheterisation and Cardiovascular Interventions: Official Journal of the Society for Cardiac Angiography & Interventions 2010; 75: 158-166.
- 14 Hobl EL, Stimpfl T, Ebner J. et al. Morphine decreases clopidogrel concentrations and effects: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol 2014; 63: 630-635.
- 15 Zeymer U, Mochmann H-C, Mark B. et al. Double-Blind, Randomized, Prospective Comparison of a Loading Dose of 60 mg Prasugrel Versus 600 mg Clopidogrel in The Early Treament Phase in Patients with Acute STEMI SCheduled for primary PCI: Results of the ETAMI Trial. J Am Coll Cardiol 2014; 63 A12
- 16 Parodi G, Valenti R, Bellandi B. et al. Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation myocardial infarction patients: RAPID (Rapid Activity of Platelet Inhibitor Drugs) primary PCI study. J Am Coll Cardiol 2013; 61: 1601-1606.
- 17 Bonello L, Tantry US, Marcucci R. et al. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 2010; 56: 919-933.
- 18 Bonello L, Paganelli F, Arpin-Bornet M. et al. Vasodilator-stimulated phosphoprotein phosphorylation analysis prior to percutaneous coronary intervention for exclusion of postprocedural major adverse cardiovascular events. J Thromb Haemost 2007; 5: 1630-1636.
- 19 Barragan P, Bouvier JL, Roquebert PO. et al. Resistance to thienopyridines: clinical detection of coronary stent thrombosis by monitoring of vasodilatorstimulated phosphoprotein phosphorylation. Cath Cardiovasc Interv 2003; 59: 295-302.
- 20 Mehran R, Rao SV, Bhatt DL. et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011; 123: 2736-2747.
- 21 Schäfer A, Flierl U, Kössler J. et al. Early determination of clopidogrel responsiveness by platelet reactivity indexidentifies patients at risk for cardiovascular events after myocardial infarction. Thromb Haemost 2011; 106: 141-148.
- 22 Penela D, Magaldi M, Fontanals J. et al. Hypothermia in acute coronary syndrome: brain salvage versus stent thrombosis?. J Am Coll Cardiol 2013; 61: 686-687.
- 23 Joffre J, Varenne O, Bougouin W. et al. Stent thrombosis: an increased adverse event after angioplasty following resuscitated cardiac arrest. Resuscitation 2014; 85: 769-773.
- 24 Udell JA, Braunwald E, Antman EM. et al. Prasugrel versus clopidogrel in patients with ST-segment elevation myocardial infarction according to timing of percutaneous coronary intervention: a TRITON-TIMI 38 subgroup analysis (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infarction 38). J Am Coll Cardiol Cardiovas Interv 2014; 7: 604-612.
- 25 Heestermans AACM, van Werkum JW, Taubert D. et al. Impaired bioavailability of clopidogrel in patients with a ST-segment elevation myocardial infarction. Thromb Res 2008; 122: 776-781.
- 26 Wiviott SD, Trenk D, Frelinger AL. et al. Prasugrel compared with high loadingand maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention: the Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation-Thrombolysis in Myocardial Infarction 44 trial. Circulation 2007; 116: 2923-2932.
- 27 Siller-Matula JM, Trenk D, Schror K. et al. Response variability to P2Y12 receptor inhibitors: expectations and reality. J Am Coll Cardiol Cardiovasc Interv 2013; 6: 1111-1128.
- 28 Bouatou Y, Samer CF, Fontana P. et al. Evidence-Based Choice of P2Y12 Inhibitors in End Stage Renal Disease Patients: A Mini-Review. Curr Drug Metabol 2015; 16: 97-104.
- 29 Ibrahim K, Christoph M, Schmeinck S. et al. High rates of prasugrel and ticagrelor non-responder in patients treated with therapeutic hypothermia after cardiac arrest. Resuscitation 2014; 85: 649-656.
- 30 Ferreiro JL, Sanchez-Salado JC, Gracida M. et al. Impact of mild hypothermia on platelet responsiveness to aspirin and clopidogrel: an in vitro pharmacodynamic investigation. J Cardiovasc Transl Res 2014; 7: 39-46.
- 31 Orban M, Mayer K, Morath T. et al. The impact of therapeutic hypothermia on on-treatment platelet reactivity and clinical outcome in cardiogenic shock patients undergoing primary PCI for acute myocardial infarction: Results from the ISAR-SHOCK registry. Thromb Res. 2015 Epub ahead of print.