European Cooperative Study Group for Recombinant Tissue-Type Plasminogen Activator II - ECSG-6


Adjunctive heparin for coronary patency in patient receiving alteplase.


Concomitant therapy with intravenous heparin would improve coronary patency and outcome in patients treated with alteplase thrombolysis for AMI, and pretreatment with alteplase would improve patency after reocclusion in a patient who has been treated with alteplase.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 652
Mean Follow Up: 48 to 120 hours
Mean Patient Age: 56.5
Female: 13

Patient Populations:

Age > 21 and < 70 years.
Severe chest pain typical of MI ischemia persisted for > 30 minutes.
> 2 mm ST-segment elevation (60 ms after J point) in 2 or more standard frontal plane leads, or > 3mm in 2 or more precordial leads.
An infusion of alteplase could be started within 6 hours of the onset of major symptoms.


Earlier transmural myocardial infarct < 14 days before, or previous infarct in similar location.
Increased risk of hemorrhagic complications.

Primary Endpoints:

Coronary patency after 48-120 hours, as assessed by coronary angiography.

Secondary Endpoints:

Enzymatic infarct size as estimated by the cumulative release of HBDH into plasma at 72 hours.
Clinical events and bleeding complications up to 48-120 hours angiography and during the whole hospital stay.
Prevalence of echocardiographically assessed left ventricular thrombus.

Drug/Procedures Used:

Alteplase 100mg (not weight adjusted) plus aspirin 250mg intravenously, followed by 75-125mg on alternate days, plus heparin 5000 units intravenously, followed by 1,000 units hourly without dose adjustment, compared with identical regimen of alteplase.

Concomitant Medications:

Analgesia as required

Principal Findings:

Coronary patency was 83.4% for the heparin group and 74.7% for placebo. The relative risk of an occluded vessel in the heparin-treated group was 0.66% (95% confidence interval 0.47 to 0.93).

Mortality was the same in both groups.

There were non-significant trends toward a smaller enzymatic infarct size and a higher incidence of bleeding complications in the heparin group.

In patients treated with a second infusion of alteplase:
Pain and ST changes disappeared within 100 minutes (median 50).
ST changes disappeared after repeated thrombolysis.
D-dimer determinations in 15 patients increased, indicating activation of the coagulation system.
Signs of reocclusion occurred despite adequate anticoagulation with heparin in 5 of 11 patients in whom coagulation measures were available.
No excess bleeding and no intracranial hemorrhage were observed.


Concomitant intravenous heparin improves coronary patency in patients with alteplase. Retreatment with alteplase is feasible and provides an alternative to angioplasty in patients with clinical and electrocardiographic signs of reocclusion early after thrombolytic therapy.


1. Br Heart J 1992;67:122-8. Final results
2. Am J Cardiol 1993;71:524-8. Alteplase retreatment

Clinical Topics: Anticoagulation Management, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Lipid Metabolism

Keywords: Risk, Thrombolytic Therapy, Myocardial Infarction, Intracranial Hemorrhages, Chest Pain, Fibrin Fibrinogen Degradation Products, Heparin, Retreatment, Tissue Plasminogen Activator, Angioplasty

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