Efficacy of prasugrel administration immediately after percutaneous coronary intervention in ST-elevation myocardial infarction

Summary

Prasugrel, a potent thienopyridine, achieves stronger inhibition of platelet activation than clopidogrel. However, onset of inhibition is significantly delayed in patients with acute ST-elevation myocardial infarction (STEMI), as haemodynamic instability and morphine application seem to exhibit significant influence. Since rapid onset of effect was demonstrated in non-STEMI patients when prasugrel was administered only after percutaneous coronary intervention (PCI) without increasing cardiovascular event rates we assessed the efficacy of prasugrel loading immediately after PCI for STEMI instead of pre-loading before revascu-larisation. We investigated 50 consecutive patients with acute STEMI (mean age 56 ± 10 years) admitted for primary PCI. Prasugrel efficacy was assessed by platelet reactivity index (PRI; VASP assay) before, 1, 2, 4, 6, 12, and 24 hours following an oral loading dose of 60 mg immediately after PCI. High on-treatment platelet reactivity (HTPR) was de-fined as PRI>50 %. Prasugrel significantly and rapidly reduced platelet reactivity in acute STEMI patients (p<0.0001 at each time point vs control). Morphine application resulted in a significantly higher HTPR rate among patients having received morphine less than 1 hour before pra-sugrel loading (p<0.001) while concomitant metoclopramide (MCP) treatment did not significantly affect prasugrel efficacy. In conclusion, in contrast to previous reports describing a significant delay in onset of prasugrel-mediated P2Y₁₂ inhibition in acute STEMI, we observed a rapid onset with low HTPR rates comparable to those observed in stable non-STEMI patients. Prasugrel administered directly after primary PCI might therefore be a useful therapeutic strategy in patients with STEMI to provide strong and effective P2Y₁₂ inhibition.

Keywords

STEMI - prasugrel - loading - PCI - morphine

• References

• 1 Montalescot G. 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.
• 2 Task Force, Steg PG. et al. ESC Guidelines for the management of acute myo-cardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33: 2569-2619.
• 3 Task Force, Windecker S. et al. 2014 ESC/EACTS Guidelines on myocardial revascularisation: The Task Force on Myocardial Revascularisation of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2014; 35: 2541-2619.
• 4 Zeymer U. et al. Double-blind, randomized, prospective comparison of loading doses of 600 mg clopidogrel versus 60 mg prasugrel in patients with acute ST-segment elevation myocardial infarction scheduled for primary percutaneous intervention: the ETAMI trial (early thienopyridine treatment to improve primary PCI in patients with acute myocardial infarction). JACC Cardiovascular interventions 2015; 08: 147-154.
• 5 Alexopoulos D. et al. Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with ST-segment-elevation myocardial infarction. Circ Cardiovasc Intervent 2012; 05: 797-804.
• 6 Jernberg T. et al. Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease. Eur Heart J 2006; 27: 1166-1173.
• 7 Gurbel PA. et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation 2009; 120: 2577-2585.
• 8 Bonello L. 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.
• 9 Wallentin L. et al. Prasugrel achieves greater and faster P2Y12receptor-mediated platelet inhibition than clopidogrel due to more efficient generation of its active metabolite in aspirin-treated patients with coronary artery disease. Eur Heart J 2008; 29: 21-30.
• 10 Montalescot G, van’t Hof AW. Prehospital ticagrelor in ST-segment elevation myocardial infarction. N Engl J Med 2014; 371: 2339.
• 11 Alexopoulos D. P2Y12 inhibitors adjunctive to primary PCI therapy in STEMI: fighting against the activated platelets. Intern J Cardiol 2013; 163: 249-255.
• 12 Parodi G. et al. Comparison of prasugrel and ticagrelor loading doses in ST-seg-ment elevation myocardial infarction patients: RAPID (Rapid Activity of Platelet Inhibitor Drugs) primary PCI study. J Am Coll Cardiol 2013; 61: 1601-1606.
• 13 Parodi G. et al. Morphine is associated with a delayed activity of oral antiplatelet agents in patients with ST-elevation acute myocardial infarction undergoing primary percutaneous coronary intervention. Circulation Cardiovasc Interv 2014; 08 pii e001593.
• 14 Flierl U. et al. Platelet inhibition with prasugrel in patients with acute myo-cardial infarction undergoing therapeutic hypothermia after cardiopulmonary resuscitation. Thromb Haemost 2016; 115: 960-968.
• 15 Tantry US. et al. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischaemia and bleeding. J Am Coll Cardiol 2013; 62: 2261-2273.
• 16 Bonello L. et al. Vasodilator-stimulated phosphoprotein phosphorylation analysis prior to percutaneous coronary intervention for exclusion of postprocedural major adverse cardiovascular events. J Thromb Haemost 2007; 05: 1630-1636.
• 17 Barragan P. et al. Resistance to thienopyridines: clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylation. Catheter Cardiovasc Interv 2003; 59: 295-302.
• 18 Mehran R. et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011; 123: 2736-2747.
• 19 Cutlip DE. et al. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 2007; 115: 2344-2351.
• 20 ACEP, SCAI. O’Gara PT. et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 61: 485-510.
• 21 Montalescot G. et al. Effect of prasugrel pre-treatment strategy in patients undergoing percutaneous coronary intervention for NSTEMI: the ACCOAST-PCI study. J Am Coll Cardiol 2014; 64: 2563-2571.
• 22 Montalescot G. et al. Prehospital ticagrelor in ST-segment elevation myocardial infarction. N Engl J Med 2014; 371: 1016-1027.
• 23 Alexopoulos D. et al. Evolving pattern of on-prasugrel and on-ticagrelor platelet reactivity over time in ST elevation myocardial infarction patients. Intern J Car-diol 2013; 168: 629-630.
• 24 Holzer P. Opioid receptors in the gastrointestinal tract. Reg Peptides 2009; 155: 11-17.
• 25 Kubica J. et al. Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial. Eur Heart J 2016; 37: 245-252.
• 26 Hobl EL. et al. Morphine interaction with prasugrel: a double-blind, cross-over trial in healthy volunteers. Clin Res Cardiol 2016; 105: 349-355.
• 27 Meine TJ. et al. Association of intravenous morphine use and outcomes in acute coronary syndromes: results from the CRUSADE Quality Improvement Initiative. Am Heart J 2005; 149: 1043-1049.
• 28 Puymirat E. et al. Correlates of pre-hospital morphine use in ST-elevation myo-cardial infarction patients and its association with in-hospital outcomes and long-term mortality: the FAST-MI (French Registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction) programme. Eur Heart J 2016; 37: 1063-1071.
• 29 de Waha S. et al. Intravenous morphine administration and reperfusion success in ST-elevation myocardial infarction: insights from cardiac magnetic resonance imaging. Clin Res Cardiol 2015; 104: 727-734.
• 30 Xanthopoulou I. et al. Factors Affecting Platelet Reactivity 2 Hours After P2Y(1)(2) Receptor Antagonist Loading in Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction - Impact of Pain-to-Loading Time. Circulation J 2016; 80: 442-449.