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Coronary reperfusion in the clinical setting: antithrombotic support to thrombolysis in the coronary care unit

J. López-Sendón1

Department of Cardiology, Hospital Universitario Gregorio Marañon, Madrid, Spain

1 Correspondence: José López-Sendón, Coronary Care Unit Area 1200, Department of Cardiology, Hospital Gregorio Marañon, Doctor Esquerdo 46, 28007 Madrid, Spain

Abstract

In acute myocardial infarction (AMI) with ST-segment elevation the first strategy is to open the artery and re-establish coronary flow as soon and completely as possible, including the patency of the epicardial coronary arteries as well as appropriate myocardial perfusion. Thrombolysis or primary percutaneous interventions are useful to restore the coronary flow but have several limitations: in many cases myocardial perfusion is incomplete, the plaque remains active, and thrombin exposure after fragmentation of the intracoronary thrombi as well the fibrinolytic agents have a prothrombotic effect. This explains the potential benefit of using anticoagulant and antiplatelet agents as adjunctive therapy during reperfusion, although there is always risk of haemorrhagic events.

Direct antithrombin agents, including hirudin and hirulog, inhibit both free and clot-bound thrombin, and improve coronary flow compared with heparin. However, in three large trials (TIMI 9B, GUSTO-2 and HIT-4) they failed to show a significant clinical benefit over heparin. Hirulog is currently under investigation in a large trial in AMI treated with streptokinase (HERO-2).

Low-molecular-weight heparins have a higher anti-factor-IIa: anti-factor-Xa ratio than unfractionated heparin and the anticoagulation is more stable and dose-dependent, and does not require monitoring. Phase II studies have shown a higher patency and lower reoclusion rate versus heparin, and the clinical relevance of these early studies is currently under investigation (enoxaparin in ASSENT III).

Experience with glycoprotein IIb/IIIa receptor inhibitors in patients with AMI and thrombolysis is limited to phase II trials. In the TIMI 14B and SPEED trials, abciximab associated with low dose of alteplase and reteplase strikingly increased coronary patency compared with the thrombolytic arm alone and the potential use of this combined therapy is under investigation (ASSENT III and GUSTO IV).

Key Words: Myocardial infarction • thrombolysis • antithrombin drugs • low molecular weight heparins • glycoproteins IIb/IIIa inhibitors

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