ESPRIT: a European study of the prevention of reocclusion after initial thrombolysis with duteplase in acute myocardial infarction.
BACKGROUND
The goal of thrombolytic treatment in acute myocardial infarction is reperfusion of the infarct-related coronary artery. Duteplase is a double-chain recombinant tissue-type plasminogen activator. Its efficacy and safety were evaluated in patients with acute myocardial infarction treated within 4 h of onset of chest pain in this multicentre, open, non-controlled trial.


RESULTS
A total of 273 patients were enrolled and treated with duteplase 0.6 MU.kg-1 over 4 h, with concomitant oral aspirin and intravenous heparin. Coronary arteriography was performed at 60 min, 90 min and approximately 24 h after the start of duteplase infusion to assess the perfusion grade (TIMI scoring) of the infarct-related coronary artery. Safety was assessed by monitoring patients closely for bleeding and for all other adverse experiences during the 72-h study period. Reinfarction during the study period was also recorded, and deaths at any time during the period in hospital were documented. TIMI grade 2 or 3 patency of the infarct-related coronary artery at 90 min was achieved in 70% of the patients and 7% of these "patent' infarct-related coronary arteries had reoccluded by 20 to 36 h. Clinical reinfarction during the 72-h study period was observed in 7%. Total in-hospital mortality was 8%. Serious or life-threatening bleeding occurred in 4% of the patients. There was one haemorrhagic stroke, and this was fatal.


CONCLUSIONS
Weight-adjusted duteplase infusion, together with oral aspirin and intravenous heparin, in acute myocardial infarction resulted in patency of the infarct-related coronary artery and a safety profile comparable to those reported for the other form of tissue-type plasminogen activator, alteplase. However, there remains a problem with reocclusion and reinfarction after initially successful thrombolysis.
Glaxo Wellcome Research and Development, Beckenham, Kent, U.K.
A D
AD
Malcolm
M
M
Keltai
M J
MJ
Walsh
D000328:Adult; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D006493:Heparin / Q000008:administration & dosage; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012008:Recurrence; D015996:Survival Rate; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects
D011994:Recombinant Proteins; D006493:Heparin; D010959:Tissue Plasminogen Activator; D001241:Aspirin; C068645:duteplase