Acute coronary reocclusion after thrombolysis with recombinant human tissue-type plasminogen activator: prevention by a maintenance infusion.

Abstract

Twenty-nine patients with acute myocardial infarction were treated with recombinant human tissue-type plasminogen activator (rt-PA). The incidence of acute coronary reocclusion and its prevention by a maintenance infusion of rt-PA were studied. Intravenous rt-PA was given at a rate of 0.4 to 0.75 mg/kg over 60 to 120 min after angiographic documentation of complete coronary occlusion. Reperfusion was accomplished within 1 hr in 24 of 29 patients (83%) and was associated with a decrease of the plasma fibrinogen level by 20%. In a first group of 13 patients, 1 1 of whom were successfully reperfused, prevention of reocclusion was attempted with heparin anticoagulation. However, acute reocclusion within 1 hr after cessation of rt-PA was demonstrated angiographically in five of these patients (45%). Quantitative angiographic analysis indicated that acute reocclusion only occurred in patients with 80% or greater residual stenosis. In patients with less than 80% residual stenosis, heparin anticoagulation was sufficient to maintain patency during the hospital stay in four of five patients. In a second group of patients (n = 16), 13 of whom underwent reperfusion with intravenous rt-PA, seven demonstrated a residual stenosis of 80% or greater. These patients were given heparin and, in addition, 10 mg of rt-PA per hour for 4 hr. None developed acute angiographic reocclusion or clinical signs of reocclusion during the hospital stay. Repeat angiography at 10 to 14 days confirmed persistent patency in six of the seven patients. The maintenance infusion resulted in only a moderate additional drop in fibrinogen, while a steady-state plasma rt-PA level of 750 250 ng/ml was maintained. In five of the six patients with less than 80% residual stenosis maintained on heparin therapy alone, follow-up angiography demonstrated persistent patency. These findings strongly suggest that a maintenance infusion of rt-PA may prevent or greatly reduce the reocclusion rate in patients with 80% or greater residual stenosis after coronary reperfusion with rt-PA. Circulation 73, No. 2, 347-352, 1986. THROMBOLYTIC THERAPY of acute myocardial infarction with streptokinase has often not produced stable coronary patency. The reported in-hospital reocclusion rate after reperfusion with intracoronary streptokinase has ranged from 5% to 29%, with an average of 17%. '61n our investigation of 34 patients with acute myocardial infarction, reocclusion after intracoronary streptokinase was seen in 18% within 2 hr, with an additional 9% of patients experiencing reocclusion before discharge.

Thrombolytic Effects of a Novel Modified Tissue Plasminogen Activator, E6010, on Coronary Thrombosis in the Pig.

“…Clot lysis and recanalization of the occluded coronary artery induced in vivo by t-PA can be accelerated by adjunctive ther apy with antiplatelet agents such as aspirin or antithrombin agents such as heparin and hiru din (28,29). It has been reported that heparin enhances thrombolysis and maintains coronary artery-patency after the administration of t-PA (6,30). As the balance between fibrin deposi tion and lysis is a key factor for thrombosis, we administered heparin to prevent the forma tion of fibrin and its incorporation into the thrombus during thrombolysis by plasminogen activators.…”

“…This rapid clearance of t PA necessitates intravenous or intracoronary infusion of a relatively high dose in order to maintain therapeutic plasma levels. The rapid decrease in plasma level of t-PA after the ter mination of infusion may result in coronary reocclusion (6), and overdose of t-PA, which may occur with continuous infusion, may in crease the risk of hemorrhagic complications (7) t-PA derivatives with slower clearance from plasma would be effective by intravenous bolus injection and provide advantages over conventional t-PA in the treatment of acute myocardial infarction and other thrombotic diseases. E6010 is a novel modified human t PA, in which cysteine 84 in the epidermal growth factor domain is replaced by serine (8).…”

Cilostazol, a novel cyclic AMP phosphodiesterase inhibitor, prevents reocclusion after coronary arterial thrombolysis with recombinant tissue-type plasminogen activator.

“…4 -7 In particular, patients with high-grade (80% or greater) residual stenosis after thrombolytic therapy are considered to be at the greatest risk for acute reocclusion. 8 A number of antiplatelet drugs have been evaluated for their effects on reperfusion and reocclusion by thrombosis or its recurrence.…”

Thrombolysis with Intracoronary Administration of YM866, a Novel Modified Tissue-Type Plasminogen Activator, in a Canine Model of Coronary Artery Thrombosis

“…This increases the risk of systemic bleeding, and results in a high incidence of acute reocclusion (1). To eliminate these shortcomings, attempts have been made to modify the t-PA molecule, and several mutants of t-PA that have prolonged plasma half-life and that can be ad ministered by intravenous (i.v.)…”