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Platelet GP IIb-IIIa Receptor Antagonists in Primary Angioplasty: Back to the Future

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Abstract

Coronary artery disease and acute myocardial infarction still represent the leading cause of mortality in developed countries. Therefore, great efforts have been made in the last decades to improve reperfusion strategies and adjunctive antithrombotic therapies. In fact, despite optimal epicardial recanalisation, a large proportion of patients still experience impaired reperfusion and in-stent thrombosis. The adjunctive use of glycoprotein (GP) IIb-IIIa inhibitors may certainly contribute in the reduction of such complications, especially when administered in the early phase of infarction. In fact, in this phase a larger platelet composition of the thrombus and the presence of a larger amount of viable myocardium, as compared to a delayed phase, may increase the benefits from this therapy and counterbalance the potential higher risk of bleeding. A large body of evidence has been accumulated on the benefits from GP IIb-IIIa inhibitors in terms of prevention of stent thrombosis, and benefits in mortality, especially among high-risk patients and as upstream strategy. Therefore, based on current available data, GP IIb-IIIa inhibitors can be recommended as early as possible (upstream strategy) among high-risk patients, such as those with advanced Killip class or anterior myocardial infarction (MI), and those presenting within the first three hours. Even though it is not universally accepted, in our opinion this strategy should be implemented in a pre-hospital setting (in ambulance) or at first hospital admission (Emergency Room or Coronary Care Unit, irrespective of whether they are in the spoke or hub hospitals). Peri-procedural intracoronary administration of GP IIb-IIIa inhibitors has not provided additional benefits as compared to intravenous administration and therefore cannot be recommended. Even though the vast majority of trials have been conducted with abciximab, several meta-analyses comparing small molecules (mainly high-dose tirofiban rather than eptifibatide) versus abciximab showed similar angiographic and clinical results between the molecules. Several recent investigations and meta-analyses have documented the higher risk of stent thrombosis associated with bivalirudin as compared to unfractionated heparin (UFH). Being that these results are independent from the use of GP IIb-IIIa inhibitors, UFH should still remain the anticoagulation therapy of choice in ST-segment elevation myocardial infarction (STEMI) patients. Minimisation of bleeding complications by extensive use of the radial approach, in the setting of STEMI, may further contribute to the adoption of a more aggressive antithrombotic and antiplatelet therapy incorporating the use of GP IIb-IIIa inhibitors. The establishment of dedicated networks for STEMI, and the large STEMI campaign, will certainly contribute to increase the proportion of patients presenting at first medical contact within the early phase (3 h) of infarction and therefore highly suitable for a more aggressive pharmacoinvasive approach with upstream administration of GP IIb-IIIa inhibitors. In fact, although the current therapeutic targets of increased rates of timely reperfusion, mainly by primary percutaneous coronary intervention (PCI), has been achieved, a deep look into the future in the fight against MI will certainly put aborting infarction as the major desirable target to be achieved.

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Authors and Affiliations

  1. Division of Cardiology, “Maggiore della Carità” Hospital, Eastern Piedmont University “A. Avogadro”, Novara, Italy

    Giuseppe De Luca

  2. Division of Cardiology, Manzoni Hospital, Lecco, Italy

    Stefano Savonitto

  3. Department of Cardiology, Isala Hospital, Zwolle, The Netherlands

    Arnoud W. J. van’t Hof

  4. Division of Cardiology, UMC St Radbout, Njimegen University, Njimegen, The Netherlands

    Harry Suryapranata

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  1. Giuseppe De Luca
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Correspondence to Giuseppe De Luca.

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Giuseppe De Luca reports receiving speaker’s fees from Daiichi-Sankyo, Eli-Lilly, Correvio, Astra-Zeneca. Stefano Savonitto reports receiving consulting, lecture fees and research grants from Eli Lilly, Daiichi Sankyo and Correvio. Arnoud van ‘t Hof reports receiving consulting fees from Eli Lilly and Astra Zeneca, lecture fees and research grant support from the Medicines Company, Eli Lilly, Daiichi-Sankyo, Astra Zeneca and Correvio. Harry Suryapranata reports receiving speaker’s fees from Orbus-Neich.

Glossary of Trials Listed

Glossary of Trials Listed

ADMIRAL:

Abciximab before Direct Angioplasty and Stenting in Myocardial Infarction Regarding Acute and Long-Term Follow-up

AIDA STEMI:

Abciximab Intracoronary versus intravenously Drug Application in ST-Elevation Myocardial Infarction

APEX MI:

Assessment of PEXelizumab in acute Myocardial Infarction

ASSIST:

A safety and efficacy study of integrilin-facilitated versus primary percutaneous coronary intervention in ST-segment elevation myocardial infarction

ATLANTIC:

Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST Elevation Myocardial Infarction to Open the Coronary Artery

BRAVE:

Bavarian Reperfusion Alternatives Evaluation

BRIGHT:

Bivalirudin Monotherapy vs. Heparin Monotherapy vs. Heparin Plus Tirofiban in AMI Patients Undergoing Coronary Intervention

CADILLAC:

Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications

DESERT:

Drug-Eluting Stents in Primary Angioplasty

EGYPT:

Early Glycoprotein IIb-IIa inhibitors in Primary Angioplasty

EMERALD:

Enhanced Myocardial Efficacy and Recovery by Aspiration of Liberated Debris

EUROMAX:

European Ambulance Acute Coronary Syndrome Angiography

EVA-AMI:

Abciximab vs Eptifibatide in primary PCI for acute ST-segment elevation myocardial infarction

FATA:

Randomized Study on Facilitated Angioplasty With Tirofiban or Abciximab

FINESSE:

Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events

GUSTO:

Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries

HEAT-PPCI:

How Effective are Antithrombotic Therapies in Primary Percutaneous Coronary Intervention

HORIZONS:

Harmonizing Outcomes with Revascularisation and Stents in Acute Myocardial Infarction

INFUSE-MI:

Intracoronary Abciximab and Aspiration Thrombectomy in Patients with Large Anterior Myocardial Infarction

MATRIX:

Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX

MULTI-STRATETGY:

Multicentre evaluation of single high-bolus dose tirofiban versus abciximab and sirolimus-eluting versus bare metal stent in acute myocardial infarction

ON-TIME:

Ongoing Tirofiban in Myocardial Infarction Evaluation

RAPPORT:

Randomized, placebo-controlled trial of platelet glycoprotein IIb-IIIa blockade with primary angioplasty for acute myocardial infarction

SCAAR:

Swedish Coronary Angiography and Angioplasty Registry

TARGET:

Do Tirofiban and ReoPro Give Similar Efficacy Outcomes Trial

TITAN-TIMI-34:

Time to Integrilin Therapy in Acute Myocardial Infarction—Thrombolysis In Myocardial Infarction 34

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De Luca, G., Savonitto, S., van’t Hof, A.W.J. et al. Platelet GP IIb-IIIa Receptor Antagonists in Primary Angioplasty: Back to the Future. Drugs 75, 1229–1253 (2015). https://doi.org/10.1007/s40265-015-0425-7

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