Thromb Haemost 2020; 120(01): 065-074
DOI: 10.1055/s-0039-1700546
Coagulation and Fibrinolysis
Georg Thieme Verlag KG Stuttgart · New York

Efficacy and Safety of Glycoprotein IIb/IIIa Inhibitors on Top of Ticagrelor in STEMI: A Subanalysis of the ATLANTIC Trial

Anne H. Tavenier
1   Department of Cardiology, Isala, Zwolle, The Netherlands
,
Renicus S. Hermanides
1   Department of Cardiology, Isala, Zwolle, The Netherlands
,
Enrico Fabris
2   Cardiovascular Department, University of Trieste, Trieste, Italy
,
Frédéric Lapostolle
3   SAMU 93, Hôspital Avícenne, Bobigny, France
,
Johanne Silvain
4   ACTION Study Group, Pitié-Salpêtrière Hospital (AP-HP), Sorbonne University, Paris, France
,
Jurrien M. ten Berg
5   Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands
,
Jens F. Lassen
6   Department of Cardiology, Odense University Hospital, Odense, Denmark
,
Leonardo Bolognese
7   Cardiovascular Department, Azienda Ospedaliera, Toscana Sudest, Arezzo, Italy
,
Warren J. Cantor
8   Division of Cardiology, Southlake Regional Health Centre, University of Toronto, Toronto, Canada
,
Ángel Cequier
9   Heart Disease Institute, Bellvitge University Hospital, IDIBELL, University of Barcelona, Barcelona, Spain
,
Mohamed Chettibi
10   Centre Hospitalo Universitaire Frantz Fanon, Blida, Algeria
,
Shaun G. Goodman
11   Terrence Donnelly Heart Centre, St. Michael's Hospital, University of Toronto, Toronto, Canada
,
Christopher J. Hammett
12   Department of Cardiology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
,
Kurt Huber
13   3rd Department of Medicine, Cardiology and Intensive Care Medicine, Wilhelminenspital , Medical School, Sigmund Freud University, Vienna, Austria
,
Magnus Janzon
14   Department of Cardiology, Linköping University, Linköping, Sweden
15   Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
,
Béla Merkely
16   Heart and Vascular Center, Semmelweis University, Budapest, Hungary
,
Robert F. Storey
17   Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
,
Uwe Zeymer
18   Klinikum Ludwigshafen und Institut für Herzinfarktforschung, Ludwigshafen, Germany
,
Patrick Ecollan
4   ACTION Study Group, Pitié-Salpêtrière Hospital (AP-HP), Sorbonne University, Paris, France
,
Jean-Phillipe Collet
4   ACTION Study Group, Pitié-Salpêtrière Hospital (AP-HP), Sorbonne University, Paris, France
,
Frank F. Willems
19   Rijnstate Hospital, Arnhem, The Netherlands
,
Abdourahmane Diallo
20   ACTION Study Group, Statistical Unit, Lariboisière Hospital (AP-HP), Paris VII University, Paris, France
,
Eric Vicaut
20   ACTION Study Group, Statistical Unit, Lariboisière Hospital (AP-HP), Paris VII University, Paris, France
,
Christian W. Hamm
21   Kerckhoff Campus, University of Giessen, Bad Nauheim, Germany
,
Gilles Montalescot
4   ACTION Study Group, Pitié-Salpêtrière Hospital (AP-HP), Sorbonne University, Paris, France
,
Arnoud W. J. van 't Hof
1   Department of Cardiology, Isala, Zwolle, The Netherlands
22   Department of Cardiology, Zuyderland Medical Center, Heerlen, The Netherlands
23   Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands
,
ATLANTIC investigators › Institutsangaben
Weitere Informationen

Publikationsverlauf

05. Juni 2019

07. September 2019

Publikationsdatum:
21. November 2019 (online)

Abstract

Background Glycoprotein IIb/IIIa inhibitors (GPIs) in combination with clopidogrel improve clinical outcome in ST-elevation myocardial infarction (STEMI); however, finding a balance that minimizes both thrombotic and bleeding risk remains fundamental. The efficacy and safety of GPI in addition to ticagrelor, a more potent P2Y12-inhibitor, have not been fully investigated.

Methods 1,630 STEMI patients who underwent primary percutaneous coronary intervention (PCI) were analyzed in this subanalysis of the ATLANTIC trial. Patients were divided in three groups: no GPI, GPI administration routinely before primary PCI, and GPI administration in bailout situations. The primary efficacy outcome was a composite of death, myocardial infarction, urgent target revascularization, and definite stent thrombosis at 30 days. The safety outcome was non-coronary artery bypass graft (CABG)-related PLATO major bleeding at 30 days.

Results Compared with no GPI (n = 930), routine GPI (n = 525) or bailout GPI (n = 175) was not associated with an improved primary efficacy outcome (4.2% no GPI vs. 4.0% routine GPI vs. 6.9% bailout GPI; p = 0.58). After multivariate analysis, the use of GPI in bailout situations was associated with a higher incidence of non-CABG-related bleeding compared with no GPI (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.32–6.64; p = 0.03). However, routine GPI use compared with no GPI was not associated with a significant increase in bleeding (OR 1.78, 95% CI 0.88–3.61; p = 0.92).

Conclusion Use of GPIs in addition to ticagrelor in STEMI patients was not associated with an improvement in 30-day ischemic outcome. A significant increase in 30-day non-CABG-related PLATO major bleeding was seen in patients who received GPIs in a bailout situation.

Supplementary Material

 
  • References

  • 1 Valgimigli M, Biondi-Zoccai G, Tebaldi M. , et al. Tirofiban as adjunctive therapy for acute coronary syndromes and percutaneous coronary intervention: a meta-analysis of randomized trials. Eur Heart J 2010; 31 (01) 35-49
  • 2 Scarborough RM, Kleiman NS, Phillips DR. Platelet glycoprotein IIb/IIIa antagonists. What are the relevant issues concerning their pharmacology and clinical use?. Circulation 1999; 100 (04) 437-444
  • 3 Montalescot G, Antoniucci D, Kastrati A. , et al. Abciximab in primary coronary stenting of ST-elevation myocardial infarction: a European meta-analysis on individual patients’ data with long-term follow-up. Eur Heart J 2007; 28 (04) 443-449
  • 4 Neumann FJ, Kastrati A, Schmitt C. , et al. Effect of glycoprotein IIb/IIIa receptor blockade with abciximab on clinical and angiographic restenosis rate after the placement of coronary stents following acute myocardial infarction. J Am Coll Cardiol 2000; 35 (04) 915-921
  • 5 Ibrahim H, Kaltenbach LA, Hess CN. , et al. Glycoprotein IIb/IIIa inhibitor use in patients with acute myocardial infarction undergoing PCI: insights from the TRANSLATE ACS study. Catheter Cardiovasc Interv 2019; 93 (04) E204-E210
  • 6 Shimada YJ, Bansilal S, Wiviott SD. , et al; PLATO Investigators. Impact of glycoprotein IIb/IIIa inhibitors on the efficacy and safety of ticagrelor compared with clopidogrel in patients with acute coronary syndromes: analysis from the Platelet Inhibition and Patient Outcomes (PLATO) Trial. Am Heart J 2016; 177: 1-8
  • 7 Stone GW, Mehran R, Goldstein P. , et al. Bivalirudin versus heparin with or without glycoprotein IIb/IIIa inhibitors in patients with STEMI undergoing primary percutaneous coronary intervention: pooled patient-level analysis from the HORIZONS-AMI and EUROMAX trials. J Am Coll Cardiol 2015; 65 (01) 27-38
  • 8 Gargiulo G, Carrara G, Frigoli E. , et al. Bivalirudin or heparin in patients undergoing invasive management of acute coronary syndromes. J Am Coll Cardiol 2018; 71 (11) 1231-1242
  • 9 Gyöngyösi M, Domanovits H, Benzer W. , et al; ReoPro-BRIDGING Study Group. Use of abciximab prior to primary angioplasty in STEMI results in early recanalization of the infarct-related artery and improved myocardial tissue reperfusion - results of the Austrian multi-centre randomized ReoPro-BRIDGING Study. Eur Heart J 2004; 25 (23) 2125-2133
  • 10 DE Luca G, Bellandi F, Huber K. , et al. Early glycoprotein IIb-IIIa inhibitors in primary angioplasty-abciximab long-term results (EGYPT-ALT) cooperation: individual patient's data meta-analysis. J Thromb Haemost 2011; 9 (12) 2361-2370
  • 11 Montalescot G, Borentain M, Payot L, Collet JP, Thomas D. Early vs late administration of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention of acute ST-segment elevation myocardial infarction: a meta-analysis. JAMA 2004; 292 (03) 362-366
  • 12 Heestermans AA, Van Werkum JW, Hamm C. , et al. Marked reduction of early stent thrombosis with pre-hospital initiation of high-dose Tirofiban in ST-segment elevation myocardial infarction. J Thromb Haemost 2009; 7 (10) 1612-1618
  • 13 Van't Hof AW, Ten Berg J, Heestermans T. , et al; Ongoing Tirofiban In Myocardial infarction Evaluation (On-TIME) 2 study group. Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial. Lancet 2008; 372 (9638): 537-546
  • 14 Hermanides RS, Heestermans AA, Ten Berg JM. , et al. High-dose tirofiban pretreatment reduces the need for bail-out study medication in patients with ST-segment elevation myocardial infarction: results of a subgroup analysis of the On-TIME 2 trial. Heart 2011; 97 (02) 106-111
  • 15 Ibanez B, James S, Agewall S. , et al; ESC Scientific Document Group. 2017 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
  • 16 O'Gara PT, Kushner FG, Ascheim DD. , et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013; 127 (04) e362-e425
  • 17 Gurbel PA, Bliden KP, Butler K. , 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 (25) 2577-2585
  • 18 Wiviott SD, Trenk D, Frelinger AL. , et al; PRINCIPLE-TIMI 44 Investigators. Prasugrel compared with high loading- and 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 (25) 2923-2932
  • 19 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
  • 20 Montalescot G, Lassen JF, Hamm CW. , et al. Ambulance or in-catheterization laboratory administration of ticagrelor for primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: rationale and design of the randomized, double-blind Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery (ATLANTIC) study. Am Heart J 2013; 165 (04) 515-522
  • 21 Becker RC, Bassand JP, Budaj A. , et al. Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial. Eur Heart J 2011; 32 (23) 2933-2944
  • 22 Steg PG, James S, Harrington RA. , et al; PLATO Study Group. 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 (21) 2131-2141
  • 23 Wallentin L, Becker RC, Budaj A. , et al; PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361 (11) 1045-1057
  • 24 Hermanides RS, van Werkum JW, Ottervanger JP. , et al; Ongoing Tirofiban In Myocardial infarction Evaluation (On-TIME) 2 study group. The effect of pre-hospital glycoprotein IIb-IIIa inhibitors on angiographic outcome in STEMI patients who are candidates for primary PCI. Catheter Cardiovasc Interv 2012; 79 (06) 956-964
  • 25 Steg PG, van 't Hof A, Hamm CW. , et al; EUROMAX Investigators. Bivalirudin started during emergency transport for primary PCI. N Engl J Med 2013; 369 (23) 2207-2217
  • 26 Stone GW, Witzenbichler B, Guagliumi G. , et al; HORIZONS-AMI Trial Investigators. Heparin plus a glycoprotein IIb/IIIa inhibitor versus bivalirudin monotherapy and paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction (HORIZONS-AMI): final 3-year results from a multicentre, randomised controlled trial. Lancet 2011; 377 (9784): 2193-2204
  • 27 Clemmensen P, Wiberg S, Van't Hof A. , et al. Acute stent thrombosis after primary percutaneous coronary intervention: insights from the EUROMAX trial (European Ambulance Acute Coronary Syndrome Angiography). JACC Cardiovasc Interv 2015; 8 (1 Pt B): 214-220
  • 28 Cantor WJ, Madan M, O'Shea JC. , et al. Bailout use of platelet glycoprotein IIb-IIIa inhibition during coronary stent implantation: observations from the ESPRIT trial. J Invasive Cardiol 2005; 17 (07) 360-364
  • 29 Vranckx P, Frigoli E, Rothenbühler M. , et al; MATRIX Investigators. Radial versus femoral access in patients with acute coronary syndromes with or without ST-segment elevation. Eur Heart J 2017; 38 (14) 1069-1080
  • 30 Jolly SS, Yusuf S, Cairns J. , et al; RIVAL trial group. Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial. Lancet 2011; 377 (9775): 1409-1420
  • 31 Romagnoli E, Biondi-Zoccai G, Sciahbasi A. , et al. Radial versus femoral randomized investigation in ST-segment elevation acute coronary syndrome: the RIFLE-STEACS (Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Syndrome) study. J Am Coll Cardiol 2012; 60 (24) 2481-2489
  • 32 De Luca G, Suryapranata H, Ottervanger JP, Antman EM. Time delay to treatment and mortality in primary angioplasty for acute myocardial infarction: every minute of delay counts. Circulation 2004; 109 (10) 1223-1225
  • 33 Valgimigli M, Tebaldi M, Campo G. , et al; FABOLUS PRO Investigators. Prasugrel versus tirofiban bolus with or without short post-bolus infusion with or without concomitant prasugrel administration in patients with myocardial infarction undergoing coronary stenting: the FABOLUS PRO (Facilitation through Aggrastat By drOpping or shortening Infusion Line in patients with ST-segment elevation myocardial infarction compared to or on top of PRasugrel given at loading dOse) trial. JACC Cardiovasc Interv 2012; 5 (03) 268-277
  • 34 Parodi G, Xanthopoulou I, Bellandi B. , et al. Ticagrelor crushed tablets administration in STEMI patients: the MOJITO study. J Am Coll Cardiol 2015; 65 (05) 511-512
  • 35 Rollini F, Franchi F, Hu J. , et al. Crushed prasugrel tablets in patients with STEMI undergoing primary percutaneous coronary intervention: the CRUSH study. J Am Coll Cardiol 2016; 67 (17) 1994-2004
  • 36 Silvain J, Storey RF, Cayla G. , et al. P2Y12 receptor inhibition and effect of morphine in patients undergoing primary PCI for ST-segment elevation myocardial infarction. The PRIVATE-ATLANTIC study. Thromb Haemost 2016; 116 (02) 369-378
  • 37 Lapostolle F, Van't Hof AW, Hamm CW. , et al; ATLANTIC Investigators. Morphine and ticagrelor interaction in primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: ATLANTIC-morphine. Am J Cardiovasc Drugs 2019; 19 (02) 173-183
  • 38 Stone GW, Maehara A, Witzenbichler B. , et al; INFUSE-AMI Investigators. Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction: the INFUSE-AMI randomized trial. JAMA 2012; 307 (17) 1817-1826
  • 39 Kammler J, Kypta A, Hofmann R. , et al. TIMI 3 flow after primary angioplasty is an important predictor for outcome in patients with acute myocardial infarction. Clin Res Cardiol 2009; 98 (03) 165-170
  • 40 Velibey Y, Guvenc TS, Demir K. , et al. Effects of bailout tirofiban on in-hospital outcomes and long-term mortality in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous intervention. Angiology 2019; 70 (05) 431-439