Low molecular weight heparin (dalteparin) compared to unfractionated heparin as an adjunct to rt-PA (alteplase) for improvement of coronary artery patency in acute myocardial infarction-the ASSENT Plus study.
BACKGROUND
Current thrombolytic-antithrombotic regimens in acute myocardialinfarction (AMI) are limited by incomplete early coronary reperfusion and by reocclusion and reinfarction. We compared the effects of low molecular weight heparin (LMWH) versus unfractionated heparin (UFH) as an adjunct to recombinant tissue-plasminogen activator (alteplase) on coronary artery patency and clinical outcomes in AMI.


METHODS
Patients with AMI treated with alteplase (n=439) were randomised to either subcutaneous dalteparin (120 IU/kg every 12h) for 4-7 days or intravenous infusion of UFH for 48 h. Coronary angiography was performed between day 4 and hospital discharge. Clinical events and safety were evaluated until day 30.


RESULTS
Overall there were higher thrombolysis in myocardial infarction (TIMI) flows in the infarct related coronary artery in the dalteparin group (p=0.016). The predefined primary end-point, TIMI grade 3 flow, did not reach statistical significance (dalteparin 69.3% versus heparin 62.5%; p=0.163). However, TIMI 0-1 flow (13.4 versus 24.4%; p=0.006) and its combination with intraluminal thrombus (27.9 versus 42.0%; p=0.003) were less common in the dalteparin group. During the period of randomised treatment there were less myocardial reinfarctions in the dalteparin group(p=0.010) but after cessation of dalteparin there were more reinfarctions resulting in no difference in death or MI at 30 days. There were no significant differences in major bleeding or stroke after 30 days.


CONCLUSIONS
In alteplase treated AMI adjunctive dalteparin for 4-7 days seems to reduce the risk of early coronary artery occlusion and reinfarction. However, early after cessation of treatment there is a raised risk of events, which might eliminate any long-term gains.
Wallentin
Lars
L
Department of Medical Sciences, Cardiology, University Hospital, S-751 85, Uppsala, Sweden. lars.wallentin@thorax.uas.lul.se
Bergstrand
Lott
L
Dellborg
Mikael
M
Fellenius
Carin
C
Granger
Christopher B
CB
Lindahl
Bertil
B
Lins
Lars Eric
LE
Nilsson
Tage
T
Pehrsson
Kenneth
K
Siegbahn
Agneta
A
Swahn
Eva
E
D000077284:Abciximab; D000279:Administration, Cutaneous; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000925:Anticoagulants / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage; D001783:Blood Flow Velocity; D017024:Chemotherapy, Adjuvant; D017023:Coronary Angiography; D017985:Dalteparin / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D006493:Heparin / Q000008:administration & dosage*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage; D007262:Infusions, Intravenous; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D009204:Myocardial Revascularization; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D012008:Recurrence; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D016896:Treatment Outcome; D014654:Vascular Patency
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D006493:Heparin; D010959:Tissue Plasminogen Activator; D001241:Aspirin; D017985:Dalteparin; D000077284:Abciximab