fibrinolytic therapy for acute myocardial infarction full antegrade perfusion (TIMI 3

fibrinolytic therapy for acute myocardial infarction full antegrade perfusion (TIMI 3 flow) at 90 minutes occurs in only 29-54% of patients 1 reocclusion occurs in at least 12% with increased morbidity and mortality. trial has recently confirmed the early findings on patency and suggests that adjunct treatment with glycoprotein IIb/IIIa receptor antagonists may hold promise Pergolide Mesylate for the better management of myocardial infarction. Over 100 agonists including adenosine diphosphate thrombin and adrenaline may activate platelets. All act via a final common pathway of activating the glycoproteinIIb/IIIa receptors around the Pergolide Mesylate platelet surface; binding of fibrinogen to these receptors then prospects to platelet aggregation. Aspirin functions synergistically with fibrinolytic therapy to reduce mortality3 and may reduce reocclusion.4 But aspirin is a Pergolide Mesylate relatively weak antiplatelet agent and platelet activation may still continue DEPC-1 via pathways independent of thromboxane A2. However studies have shown that if ?80% of glycoprotein IIb/IIIa receptors are blocked by specific antagonists platelet aggregation is almost completely inhibited.5 Glycoprotein Iib/IIIa receptor antagonists have been found to be beneficial without fibrinolytic therapy Pergolide Mesylate in clinical trials of over 30?000 patients with unstable angina or non-Q wave myocardial infarction. Thus IIb/IIIa receptor antagonists have been studied in acute myocardial infarction as adjuncts to fibrinolytic therapy to see if they improved reperfusion and prevent reocclusion. Early preclinical studies were conducted using the F(ab) fragment of the murine monoclonal 7E3 antibody to the IIb/IIIa receptor (m7E3). Later as m7E3 was found to be immunogenic a human constant region IgG was combined with the mouse derived variable region F(ab) thereby forming chimeric (c)7E3 or “abciximab.” In coronary thrombus models use of m7E3 or c7E3 together with fibrinolytic brokers improved reperfusion6 7 and reduced reocclusion6-8 when compared with standard fibrinolytic therapy (with or without antiplatelet therapy). The first clinical study the TAMI 8 pilot study enrolled 70 patients with acute myocardial infarction.9 All received aspirin heparin and alteplase and 60 were also given m7E3 boluses at 3 6 and 15 hours after the alteplase. Those receiving m7E3 showed greater patency in the culprit artery than the controls (92% 56%); they had less recurrent ischaemia (13% 20%) and no excess bleeding. The IMPACT-AMI trial enrolled 180 patients with acute myocardial infarction.10 All received aspirin heparin and alteplase and were randomised (132 open label) to eptifibatide (a cyclic heptapeptide IIb/IIIa antagonist) or placebo. Those treated with high dose eptifibatide experienced improved TIMI 3 circulation at 90 moments (66% 39%; P=0.006) and a shorter median time to ST segment recovery (65 116 min; P=0.05). The PARADIGM trial enrolled 353 patients with acute myocardial infarction.11 All but three received aspirin heparin and fibrinolytic therapy (alteplase or streptokinase). In an initial dose finding phase 30 patients were given open label lamifiban (a non-peptide IIb/IIIa antagonist). Subsequent patients were randomised double blind to lamifiban or placebo. Those receiving lamifiban experienced shorter time to constant state ST resolution (88 122 min; P=0.003) but more major bleeding (3% 1.7%). The largest randomised clinical trial (TIMI 14)-888 patients with acute myocardial infarction-has recently been published.12 Patients received aspirin and heparin (all but six) and were randomised to one of four open label reperfusion regimens: 100 mg alteplase alone (control); abciximab (0.25 mg/kg bolus 0.125 μg/kg/min 12 hour infusion) alone; abciximab with reduced doses of alteplase; or abciximab with reduced doses of streptokinase. In an initial dose finding phase (677 patients) TIMI 3 circulation at 90 moments was 57% for alteplase alone 32 for abciximab alone 34 for abciximab plus streptokinase (0.5-1.25 MU) and 38-76% for Pergolide Mesylate abciximab plus alteplase (20-65 mg). The incidence of major haemorrhage was comparable in those receiving alteplase alone (6%) and abciximab plus alteplase (7%) but higher in those receiving abciximab plus streptokinase (10%). The overall rate Pergolide Mesylate of intracranial haemorrhage was 1.1%. In a dose confirmation phase 211 patients.