A RANDOMIZED DOSE-RANGING STUDY OF RT-PA IN ACUTE MYOCARDIAL-INFARCTION - EFFECTS ON CORONARY PATENCY AND FIBRINOLYTIC PARAMETERS

This study was designed to examine the relationships between dose of Wellcome two-chain recombinant tissue type-plasminogen activator (BW rt-PA) and coronary patency and fibrinolytic parameters in acute myocardial infarction (AMI). In an open randomized study, patients with AMI (determined by ECG) and symptoms of less than 4 h duration without contraindications for fibrinolytic therapy were treated with rt-PA in nominal doses of 20 (7·7 MU), 50 (14·8-29·6 MU) or 100 mg (29·6-48·2 MU) administered over 90 min followed by intravenous heparin. Coronary patency was determined by coronary arteriography of the infarct-related artery and haematological parameters (fibrinogen, plasminogen, α2-antiplasmin and fibrin (ogen) degradation products) measured at 90 min. Coronary patency increased in a dose-related manner to 53% (95% C.I. 37-69%) in the 100 mg/90 min group. Logistic regression demonstrated a relationship between dose (in MU kg-1) and coronary patency. Fibrinogen at 90 m was reduced to 74 (61·5-86·4%) of the pooled plasma standard in the nominal 100 mg group. Patients with a higher predose fibrinogen had higher reductions of fibrinogen. Serious bleeding occurred in three (3%) patients, and no intracranial bleeds were reported. BW rt-PA produces dose-related patency of the coronary arteries with moderate, dose-related reduction in fibrinogen. © 1990 The European Society of Cardiology.