Cangrelor versus Ticagrelor in Patients Treated with Primary Percutaneous Coronary Intervention: Impact on Platelet Activity, Myocardial Microvascular Function and Infarct Size: A Randomized Controlled Trial

Abstract

Background Oral P2Y12 inhibitors take more than 2 hours to achieve full effect in healthy subjects and this action is further delayed in patients with acute myocardial infarction. Intravenous P2Y12 inhibition might lead to more timely and potent anti-platelet effect in the context of emergency primary angioplasty, improving myocardial recovery.

Objectives This article compares the efficacy of intravenous cangrelor versus ticagrelor in a ST-elevation myocardial infarction (STEMI) population treated with primary percutaneous coronary intervention (PPCI).

Materials and Methods In an open-label, prospective, randomized controlled trial, 100 subjects with STEMI were assigned 1:1 to intravenous cangrelor or oral ticagrelor. The co-primary endpoints were platelet P2Y12 inhibition at infarct vessel balloon inflation time, 4 and 24 hours. Secondary endpoints included indices of coronary microcirculatory function: index of microvascular resistance (IMR), initial infarct size (troponin at 24 hours) and final infarct size at 12 weeks (cardiac magnetic resonance). Secondary endpoints included indices of coronary microcirculatory function (index of microvascular resistance [IMR]), initial infarct size (troponin at 24 hours), final infarct size at 12 weeks (cardiac magnetic resonance), corrected thrombolysis in myocardial infarction (TIMI) frame count, TIMI flow grade, myocardial perfusion grade, and ST-segment resolution (ClinicalTrials.gov NCT02733341).

Results P2Y12 inhibition at first balloon inflation time was significantly greater in cangrelor-treated patients (cangrelor P2Y12 reaction unit [PRU] 145.2 ± 50.6 vs. ticagrelor 248.3 ± 55.1). There was no difference in mean PRU at 4 and 24 to 36 hours post-dosing. IMR, final infarct size, angiographic and electrocardiographic measures of reperfusion were all similar between groups.

Conclusion Cangrelor produces more potent P2Y12 inhibition at the time of first coronary balloon inflation time compared with ticagrelor. Despite this enhanced P2Y12 inhibition, coronary microvascular function and final infarct size did not differ between groups.

Keywords

anti-platelet - infarct size - microcirculation - myocardial infarction - percutaneous coronary intervention

• References

• 1 Ibanez B, James S, Agewall S. , et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2018; 39 (02) 119-177
• 2 Sibbing D, Kastrati A, Berger PB. Pre-treatment with P2Y12 inhibitors in ACS patients: who, when, why, and which agent?. Eur Heart J 2016; 37 (16) 1284-1295
• 3 Franchi F, Rollini F, Angiolillo DJ. Antithrombotic therapy for patients with STEMI undergoing primary PCI. Nat Rev Cardiol 2017; 14 (06) 361-379
• 4 Alexopoulos D, Pappas C, Sfantou D. , et al. Cangrelor in ticagrelor-loaded STEMI patients undergoing primary percutaneous coronary intervention. J Am Coll Cardiol 2018; 72 (14) 1750-1751
• 5 Franchi F, Rollini F, Rivas A. , et al. Platelet inhibition with cangrelor and crushed ticagrelor in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: results of the CANTIC Study. Circulation 2019; 139 (14) 1661-1670
• 6 Capodanno D, Angiolillo DJ. Antiplatelet therapy after implantation of bioresorbable vascular scaffolds: a review of the published data, practical recommendations, and future directions. JACC Cardiovasc Interv 2017; 10 (05) 425-437
• 7 Carrick D, Haig C, Ahmed N. , et al. Comparative prognostic utility of indexes of microvascular function alone or in combination in patients with an acute ST-segment-elevation myocardial infarction. Circulation 2016; 134 (23) 1833-1847
• 8 Brener SJ, Maehara A, Dizon JM. , et al. Relationship between myocardial reperfusion, infarct size, and mortality: the INFUSE-AMI (Intracoronary Abciximab and Aspiration Thrombectomy in Patients With Large Anterior Myocardial Infarction) trial. JACC Cardiovasc Interv 2013; 6 (07) 718-724
• 9 Morishima I, Sone T, Okumura K. , et al. Angiographic no-reflow phenomenon as a predictor of adverse long-term outcome in patients treated with percutaneous transluminal coronary angioplasty for first acute myocardial infarction. J Am Coll Cardiol 2000; 36 (04) 1202-1209
• 10 Porto I, Biasucci LM, De Maria GL. , et al. Intracoronary microparticles and microvascular obstruction in patients with ST elevation myocardial infarction undergoing primary percutaneous intervention. Eur Heart J 2012; 33 (23) 2928-2938
• 11 Price MJ, Angiolillo DJ, Teirstein PS. , et al. Platelet reactivity and cardiovascular outcomes after percutaneous coronary intervention: a time-dependent analysis of the Gauging Responsiveness with a VerifyNow P2Y12 assay: Impact on Thrombosis and Safety (GRAVITAS) trial. Circulation 2011; 124 (10) 1132-1137
• 12 Fearon WF, Balsam LB, Farouque HM. , et al. Novel index for invasively assessing the coronary microcirculation. Circulation 2003; 107 (25) 3129-3132
• 13 Gupta A, Taqueti VR, van de Hoef TP. , et al. Integrated noninvasive physiological assessment of coronary circulatory function and impact on cardiovascular mortality in patients with stable coronary artery disease. Circulation 2017; 136 (24) 2325-2336
• 14 Appleby MA, Michaels AD, Chen M, Michael CG. Importance of the TIMI frame count: implications for future trials. Curr Control Trials Cardiovasc Med 2000; 1 (01) 31-34
• 15 de Lemos JA, Braunwald E. ST segment resolution as a tool for assessing the efficacy of reperfusion therapy. J Am Coll Cardiol 2001; 38 (05) 1283-1294
• 16 McAlindon E, Pufulete M, Lawton C, Angelini GD, Bucciarelli-Ducci C. Quantification of infarct size and myocardium at risk: evaluation of different techniques and its implications. Eur Heart J Cardiovasc Imaging 2015; 16 (07) 738-746
• 17 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 (23) 2736-2747
• 18 Hochholzer W, Kleiner P, Younas I. , et al. Randomized comparison of oral P2Y₁₂-receptor inhibitor loading strategies for transitioning from cangrelor: the ExcelsiorLOAD2 Trial. JACC Cardiovasc Interv 2017; 10 (02) 121-129
• 19 Frossard M, Fuchs I, Leitner JM. , et al. Platelet function predicts myocardial damage in patients with acute myocardial infarction. Circulation 2004; 110 (11) 1392-1397
• 20 Campo G, Valgimigli M, Gemmati D. , et al. Value of platelet reactivity in predicting response to treatment and clinical outcome in patients undergoing primary coronary intervention: insights into the STRATEGY Study. J Am Coll Cardiol 2006; 48 (11) 2178-2185
• 21 Velders MA, Abtan J, Angiolillo DJ. , et al; PLATO Investigators. Safety and efficacy of ticagrelor and clopidogrel in primary percutaneous coronary intervention. Heart 2016; 102 (08) 617-625
• 22 Kunadian V, James SK, Wojdyla DM. , et al. Angiographic outcomes in the PLATO Trial (Platelet Inhibition and Patient Outcomes). JACC Cardiovasc Interv 2013; 6 (07) 671-683
• 23 Montalescot G, van 't Hof AW, Lapostolle F. , et al; ATLANTIC Investigators. Prehospital ticagrelor in ST-segment elevation myocardial infarction. N Engl J Med 2014; 371 (11) 1016-1027
• 24 Alexopoulos D, Gkizas V, Patsilinakos S. , et al. Double versus standard loading dose of ticagrelor: onset of antiplatelet action in patients with STEMI undergoing primary PCI. J Am Coll Cardiol 2013; 62 (10) 940-941
• 25 Alexopoulos D, Barampoutis N, Gkizas V. , et al. Crushed versus integral tablets of ticagrelor in ST-segment elevation myocardial infarction patients: a randomized pharmacokinetic/pharmacodynamic study. Clin Pharmacokinet 2016; 55 (03) 359-367
• 26 Steg PG, Bhatt DL, Hamm CW. , et al; CHAMPION Investigators. Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patient-level data. Lancet 2013; 382 (9909): 1981-1992
• 27 Costantini CO, Stone GW, Mehran R. , et al. Frequency, correlates, and clinical implications of myocardial perfusion after primary angioplasty and stenting, with and without glycoprotein IIb/IIIa inhibition, in acute myocardial infarction. J Am Coll Cardiol 2004; 44 (02) 305-312