Third Thrombolysis Trial of Anistreplase (Eminase®) in Acute myocardial infarction - TEAM-3


Anistreplase vs. alteplase for LV function and coronary patency in acute MI.


Detect a clinically significant point difference (3%) in convalescent ejection fraction (at discharge and one month) between the APSAC and rt-PA treatment groups.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 325
Mean Follow Up: 1 month
Mean Patient Age: 58
Female: 26
Mean Ejection Fraction: At 1-month follow-up (performed at 38 ±1.7 days), 50.2% in APSAC group vs. 54.8% in the rt-PA group (p = 0.002).

Patient Populations:

Ischemic pain lasting >30 minutes and could be treated within 4 hours of its onset.
ECG ST-segment elevation in two or more contiguous leads that was >0.1 mV in at least one limb lead or >0.2 mV in at least one precordial lead.
Chest pain and ECG changes that were not completely relieved by IV or sublingual administration of nitroglycerin if this treatment was not contraindicated.
Could undergo radionuclide ventriculography within 4 hours of the start of therapy.
Ability to give informed consent.


Age >76 years
Active internal bleeding or history of hemorrhagic diathesis.
History (at any time) of a cerebrovascular accident, intracranial neoplasm, arteriovenous fistula or aneurysm<.BR> Recent (within 6 months) intracranial or intraspinal surgery or trauma.
Recent (within 3 months) gastrointestinal or genitourinary bleeding.
Operation within 10 days that could predispose to life-threatening bleeding.
Sustained or traumatic external chest massage (e.g., >2 minutes duration, rib fractures) or other significant trauma (e.g., head injury, traumatic intubation).
Recent (within 6 months) severe, uncontrolled hypertension, significant hypertensive complications (e.g., hypertensive encephalopathy, lacunar infarction).
Systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg on admission.
Ongoing cardiogenic shock (systolic blood pressure <80 mmHg, or pressor or intra-aortic balloon dependency or Killip class IV status.
Receipt of streptokinase or APSAC within 6 months or severe allergic reaction to streptokinase, APSAC or rt-PA.
Recent history (within 1 month) of coronary angioplasty or history of bypass graft surgery.
Long-term therapy with full-dose anticoagulant agents (e.g., warfarin, heparin).
Prosthetic valves, dilated cardiomyopathy or ventricular aneurysm.
Pregnancy, lactation or childbearing potential.

Primary Endpoints:

Convalescent left ventricular ejection fraction (rest function)

Secondary Endpoints:

Convalescent left ventricular ejection fraction (exercise function), clinical morbidity, coronary artery patency at one day, death, stroke (hemorrhagic, thrombotic or embolic), reinfarction, congestive heart failure, ventricular fibrillation, emergency coronary artery bypass graft (CABG), ischemic pain, ventricular tachycardia.

Drug/Procedures Used:

APSAC, 30 U/2-5 minutes IV; or rt-PA, 10 mg IV bolus, 50 mg over 1 hour then 20 mg/hour over 2 hours. For patients weighing >65 kg, 1.25 mg/kg total dose.

Concomitant Medications:

Heparin, 5000 U IV bolus 2 hours after start of thrombolysis then 100 U/hour adjusted to activated partial thromboplastin times 1.5-2.5 times normal for 2 days; aspirin, 160-325 mg/day orally for 1 month

Principal Findings:

Convalescent ejection fraction at the predischarge study averaged 51.3% in the APSAC group and 54.2% in the rt-PA group (p less than 0.05); at 1 month, ejection fraction averaged 50.2% vs. 54.8%, respectively (p less than 0.01).

In contrast, ejection fraction showed similar augmentation with exercise at 1 month after APSAC (+4.3% points) and rt-PA (+4.6% points), and exercise times were comparable.

Coronary artery patency at 1 day was high and similar in both groups (APSAC 89%, rt-PA 86%).

Mortality (APSAC 6.2%, rt-PA 7.9%) and the incidence of other serious clinical events, including stroke, ventricular tachycardia, ventricular fibrillation, heart failure within 1 month, recurrent ischemia and reinfarction were comparable in the two groups; and mechanical interventions were applied with equal frequency.

A combined clinical morbidity index was determined and showed a comparable overall outcome for the two treatments.

TIMI Perfusion grades for the entire study population were distributed as 12% (n = 37) grades 0/1, 13% (n = 40) grade 2, and 74% (n = 221) grade 3.

Further coronary interventions were performed after the 1-day patency determination in 43% of patients (43%, 48%, 42%, respectively, in TIMI Perfusion grades 0/1, 2, and 3 patients). The outcome of TIMI Perfusion grade 2 patients did not differ from grades 0/1 patients in ejection fraction, enzyme peaks, ECG markers, or morbidity index.

In contrast, TIMI Perfusion grade 3 patients, compared with grades 0-2 patients, showed the following:
A greater global ejection fraction at 1 week (54% vs. 49%, p = 0.006) and at 1 month (54% vs. 49%, p = 0.01).
A greater infarct zone ejection fraction at 1 week (41% vs. 33%, p = 0.003) and at 1 month (42% vs. 32%, p = 0.003).
Smaller enzyme peaks, significant for lactate dehydrogenase, and shorter times to enzyme peaks, significant for all four enzymes.
A smaller QRS score at discharge and at 1 month.
A trend toward a lower morbidity index.

In patients treated with APSAC, coronary patency rates were similar in those in the upper quintile of body weight (> 94 kg; n = 22) and in the low-normal weight group (n = 126) (86 and 90%, respectively, for TIMI Perfusion grade 2/3 [p = 0.64]; and 82 and 74%, respectively, for TIMI Perfusion grade 3 [p = 0.42]).

In contrast, for the rt-PA group, heavy patients (n = 34) achieved significantly lower patency rates (74 vs. 89% for TIMI Perfusion grade 2/3 [p = 0.02]; and 59 vs. 77% for TIMI Perfusion grade 3 [p = 0.03]).

The dose of heparin administered, adjusted to maintain a therapeutic partial thromboplastin time until the 1-day (mean 28 hours) angiogram, was greater in the heavy than in the low-normal weight group (mean ±SE 39,680 ±4,818 vs. 30,027 ±1,177 U; p = 0.007).


Convalescent rest ejection fraction was high after both therapies but higher after rt-PA; other clinical outcomes, including exercise function, morbidity index, and 1-day coronary artery patency, were favorable and comparable after APSAC and rt-PA.

TIMI Perfusion grade 3 flow predicts significantly better outcomes than lesser grades of flow and represents an important measure of reperfusion success.

Coronary artery patency rates at one day are not adversely affected in heavy patients who receive standard doses of APSAC, but are lower after standard doses of rt-PA. This suggests that larger doses of rt-PA or heparin, or both, may be needed to achieve optimal patency outcome.


1. J Am Coll Cardiol 1992;20:753-66. Final results
2. Circulation 1993;87:1829-39. TIMI flow and outcome
3. Am J Cardiol 1994;73:16-22. Body weight and reperfusion

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, SCD/Ventricular Arrhythmias, Lipid Metabolism, Novel Agents, Acute Heart Failure, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Myocardial Infarction, Stroke, Ventricular Fibrillation, Body Weight, Heparin, Fibrinolytic Agents, Electrocardiography, Tachycardia, Ventricular, Radionuclide Ventriculography, Chest Pain, Heart Failure, Partial Thromboplastin Time, Anistreplase, L-Lactate Dehydrogenase, Coronary Vessels, Informed Consent, Tissue Plasminogen Activator, Nitroglycerin

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