Cangrelor in ST-Elevation Myocardial Infarction to Decrease Infarct Size

Periprocedural Cangrelor in Patients With ST-Elevation Myocardial Infarction to Reduce Development of Myocardial Necrosis

This study evaluates differences in the extent of myocardial necrosis noted by cardiac MRI in patients with ST-elevation myocardial infarction randomized to receive cangrelor during their percutaneous coronary intervention and compares them to patients randomized to not receive cangrelor.

Cangrelor is a direct-acting and reversible intravenously administered platelet inhibitor approved as an adjunct to percutaneous intervention (PCI) for reducing the risk of periprocedural myocardial infarction, repeat coronary revascularization, and stent thrombosis. As it has a quick onset of action (2 minutes) compared to traditional oral platelet inhibitors, cangrelor is emerging as an important new option for use in patients undergoing percutaneous intervention who have not been treated with oral platelet inhibitors. Furthermore, multiple studies have demonstrated that patients with ST-elevation myocardial infarction (STEMI) who undergo emergent PCI do not have optimal platelet inhibition even after administration of a loading dose of traditional oral platelet inhibitors. However, the clinical significance of complete platelet inhibition around the time of PCI is not fully understood. The primary objective is to characterize the utility of immediate platelet inhibition with intravenous cangrelor in patients presenting with an acute STEMI by assessing the extent of infarct size (either enzymatically or by imaging). If the findings are favorable, this may suggest that immediate platelet inhibition is an important part of care in this patient population.

Approximately 30 patients in this arm will receive standard STEMI care but will also receive standard dosing of cangrelor at the time of their PCI.

Approximately 30 patients in this arm will receive standard STEMI but will not receive cangrelor at the time of their PCI.

Cangrelor 30 mcg/kg bolus followed by a 4 mcg/kg/min intravenous infusion prior to PCI will be given. It will be continued for ≥ 2 hours or for the duration of the procedure, whichever is longer.

Cardiac MRI is obtained at 48 hours and 3 months to compare differences in infarct size. The outcome is assessed as the difference in infarct size between 48 hours and 3 months in each group.

Flow cytometry on peripheral blood will be performed to quantify peripheral counts of inflammatory cells, stem cells, and monocyte subtypes.

ELISA assay will be performed on plasma to quantify the amount of the inflammatory cytokine interleukin-6 in pg/mL.

Inclusion Criteria: Patients with an acute STEMI with the University of Kentucky as the institution of presentation with plans for PCI English-speaking Exclusion Criteria: Pregnant patients Prisoners Patients who are unable to provide his/her own consent Patients with a prior history of myocardial infarction Patients who have received thrombolytics Patients on systemic anticoagulation Patients who are hemodynamically unstable with evidence of shock Patients who are mechanically intubated Patients with devices not MRI compatible Patients with chronic kidney disease, glomerular filtration rate less than 30 Patients who are already on dual antiplatelet therapy

Keating GM. Cangrelor: A Review in Percutaneous Coronary Intervention. Drugs. 2015 Aug;75(12):1425-34. doi: 10.1007/s40265-015-0445-3.

Johnson TW, Mumford AD, Scott LJ, Mundell S, Butler M, Strange JW, Rogers CA, Reeves BC, Baumbach A. A Study of Platelet Inhibition, Using a 'Point of Care' Platelet Function Test, following Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction [PINPOINT-PPCI]. PLoS One. 2015 Dec 16;10(12):e0144984. doi: 10.1371/journal.pone.0144984. eCollection 2015.

Parodi G, Valenti R, Bellandi B, Migliorini A, Marcucci R, Comito V, Carrabba N, Santini A, Gensini GF, Abbate R, Antoniucci D. 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 Apr 16;61(15):1601-6. doi: 10.1016/j.jacc.2013.01.024. Epub 2013 Mar 22.

Sibbing D, Braun S, Morath T, Mehilli J, Vogt W, Schomig A, Kastrati A, von Beckerath N. Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. J Am Coll Cardiol. 2009 Mar 10;53(10):849-56. doi: 10.1016/j.jacc.2008.11.030.

Stone GW, Maehara A, Witzenbichler B, Godlewski J, Parise H, Dambrink JH, Ochala A, Carlton TW, Cristea E, Wolff SD, Brener SJ, Chowdhary S, El-Omar M, Neunteufl T, Metzger DC, Karwoski T, Dizon JM, Mehran R, Gibson CM; INFUSE-AMI Investigators. Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction: the INFUSE-AMI randomized trial. JAMA. 2012 May 2;307(17):1817-26. doi: 10.1001/jama.2012.421. Epub 2012 Mar 25.

Abo-Aly M, George B, Shokri E, Chelvarajan L, El-Helw M, Smyth SS, Abdel-Latif A, Ziada K. Cangrelor in addition to standard therapy reduces cardiac damage and inflammatory markers in patients with ST-segment elevation myocardial infarction. J Thromb Thrombolysis. 2021 Oct;52(3):934-940. doi: 10.1007/s11239-020-02345-8. Epub 2020 Nov 30.