http://repub.eur.nl/res/aut/4648/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/12884/ 2000-09-30T00:00:00Z AIMS: Thrombolytic therapy restores coronary patency in patients with acute myocardial infarction, although normal perfusion (TIMI 3 flow) is not achieved in all patients. In an attempt to improve TIMI 3 flow, a combination of full-dose streptokinase, aspirin and escalating dosages of a platelet glycoprotein IIb/IIIa receptor blocker, eptifibatide, vs placebo were tested. METHODS AND RESULTS : A bolus of 180 microg. kg(-1)of eptifibatide was administered in each group, followed by a 72 h continuous infusion of 0.75 (44 patients), 1.33 (n=45) and 2.00 microg. kg(-1). min(-1)(n = 30); 62 patients received placebo. Normal perfusion (TIMI 3 flow) at 90 min was observed in 31% of placebo patients compared to 46, 42 and 45% in the ascending eptifibatide groups (44% for combined eptifibatide groups, P = 0.07). Patency (TIMI 2 and 3 flow combined) increased from 61% (placebo) to 78% for the combined eptifibatide groups (P = 0.02). Reocclusion was infrequent. No differences were observed in TIMI flow grades among eptifibatide groups. Major and minor bleeding was increased and occurred mainly at the arterial puncture site. CONCLUSION: A combination of full dose streptokinase with different eptifibatide regimens enhanced coronary perfusion, but bleeding risk was excessive. Additional trials are needed with different dosage regimens to determine the optimal combination of fibrinolytic agents and platelet glycoprotein IIb/IIIa receptor blockers. http://repub.eur.nl/res/pub/5521/ 1996-01-01T00:00:00Z BACKGROUND: The recent international GUSTO trial of 41,021 patients with acute myocardial infarction demonstrated improved 90-min infarct related artery patency as well as reduced mortality in patients treated with an accelerated regimen of tissue plasminogen activator, compared to patients treated with streptokinase. A regimen combining tissue plasminogen activator and streptokinase yielded intermediate results. The present study investigated the effects of treatment on infarct size and enzyme release kinetics in a subgroup of these patients. METHODS: A total of 553 patients from 15 hospitals were enrolled in the study. Four thrombolytic strategies were compared: streptokinase with subcutaneous heparin, streptokinase with intravenous (i.v.) heparin, tissue plasminogen activator with i.v. heparin, and streptokinase plus tissue plasminogen activator with i.v. heparin. The activity of alpha-hydroxybutyrate dehydrogenase (HBDH) in plasma was centrally analysed and infarct size was defined as cumulative HBDH release per litre of plasma within 72 h of the first symptoms (Q(72)). Patency of the infarct-related vessel was determined by angiography in 159 patients, 90 min after treatment. RESULTS: Infarct size was 3.72 g-eq.1(-1) in patients with adequate coronary perfusion (TIMI-3) at the 90 min angiogram and larger in patients with TIMI-2 (4.35 g-eq.1(-1) or TIMI 0-1 (5.07 g-eq.1(-1) flow (P = 0.024). In this subset of the GUSTO angiographic study, early coronary patency rates (TIMI 2 + 3) were similar in the two streptokinase groups (53 and 46%). Higher, but similar, patency rates were observed in the tissue plasminogen activator and combination therapy groups (87 and 90%). Median infarct size for the four treatment groups, expressed in gram-equivalents (g-eq) of myocardium, was 4.4, 4.5, 3.9 and 3.9 g-eq per litre of plasma (P = 0.04 for streptokinase vs tissue plasminogen activator). Six hours after the first symptoms, respectively 5.3, 6.6, 14.0 and 13.6% of total HBDH release was complete (P < 0.0001 for streptokinase vs tissue plasminogen activator). CONCLUSIONS: Rapid and complete coronary reperfusion salvages myocardial tissue, resulting in limitation of infarct size and accelerated release of proteins from the myocardium. Treatment with tissue plasminogen activator, resulting in earlier reperfusion was more effective in reducing infarct size than the streptokinase regimens, which contributes to the differences in survival between treatment groups in the GUSTO trial.