[New strategies in the treatment of acute myocardial infarction].
A number of experimental and clinical studies have recently underlined the importance, in acute myocardial infarction, of platelet adhesion and aggregation after plaque rupture. During clot resolution, platelet-rich thrombi are relatively resistant to fibrinolytic agents, mainly due to the release of plasminogen inhibitor-1 by platelets which are activated as a result of the increase in thrombin generation induced by plasminogen activator therapy despite heparin administration. Platelet glycoprotein (GP) IIb/IIIa integrin receptor blockers prevent platelet aggregation by blocking the final pathway of platelet activation. Thus, they also prevent the formation of an intraluminal white thrombus without affecting adhesion. Animal and human studies have shown that the potent inhibition of platelet GP IIb/IIIa receptors can lead to modest reperfusion rates even without exogenous fibrinolytic therapy. This suggests that combining the "dethrombotic" effects of a GP IIb/IIIa antagonist with lower fibrynolytic doses may result in a synergistic effect. Preclinical studies including patients with myocardial infarction have shown that such combined treatment increases the incidence, speed and durability of reperfusion. It has also been proved to be useful in improving the microcirculatory coronary flow and in facilitating subsequent percutaneous coronary interventions. In the phase III GUSTO V trial, abciximab combined with 5 + 5 U of reteplase and low-dose weight-adjusted heparin led to a 30-day mortality rate that was similar to that obtained with full-dose reteplase (10 + 10 U) and standard heparin therapy, without causing a significant increase in the incidence of intracranial hemorrhage. The results of this trial offer a rationale for alternative reperfusion therapy, although further analyses, including a 1-year follow-up, are needed to define the patient groups that are most likely to benefit from such a new regimen.
Gonzi
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Divisione di Cardiologia Dipartimento del Cuore Ospedale Maggiore Via Gramsci, 14 43100 Parma.
Ardissino
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D
D017130:Angioplasty / Q000379:methods; D000818:Animals; D002986:Clinical Trials as Topic; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008833:Microcirculation; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D013927:Thrombosis / Q000139:chemically induced / Q000188:drug therapy
D005343:Fibrinolytic Agents; D019039:Platelet Glycoprotein GPIIb-IIIa Complex