Thrombolysis and Angioplasty in Myocardial Infarction - phase V - TAMI-5


Multiple thrombolytic and PTCA strategies for acute MI.


Combination drug therapy and aggressive PTCA would lead to better global left ventricular function as measured by ejection fraction.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 575
Mean Follow Up: 5 to 10 days
Mean Patient Age: 57.5
Female: 24
Mean Ejection Fraction: Almost identical (54%) at predischarge PTCA, no matter whether PTCA or thrombolytic therapy was used (p = 0.98).

Patient Populations:

Symptoms compatible with acute myocardial infarction (AMI) of six hours duration or less accompanied by an ECG with more than 1 mm (0.1 mV) ST-segment elevation in two or more contiguous leads
<76 years old.
No contraindication to thrombolytic intervention, including previous stroke or other known cranial disease, recent trauma or surgery, refractory hypertension, active bleeding, or prolonged (more than 10 minutes)cardiopulmonary resuscitation.
No previous coronary artery bypass graft (CABG).
No previous Q wave infarction in the same distribution as the current infarction.
Absence of cardiogenic shock as defined as systolic blood pressure of less than 80 mmHg with vasopressor requirement.

Primary Endpoints:

Composite clinical endpoint: death, stroke, reinfarction, reocclusion, heart failure, recurrent ischemia, or none of the above.

Drug/Procedures Used:

Urokinase, 1.5 x 106 U IV bolus followed by 1.5 x 106 U infusion over 90 minutes; recombinant tissue-type plasminogen activator (rt-PA), 100 mg over 3 hours (given as 6 mg bolus followed by 60 mg over 1 hour then a 20 mg infusion in each of the subsequent 2 hours); or combination therapy with urokinase, 1.5 x 106 U over 1 hour plus rt-PA, 1 mg/kg (10% given as a bolus and a maximum dose of 90 mg) over 1 hour. Immediate catheterization with PTCA for failed thrombolysis, or deferred predischarge PTCA between day 5 and day 10.

Concomitant Medications:

Aspirin, 325 mg/day orally. At the end of the thrombolytic therapy, heparin infusion, 1000 U/hour continued for at least 48 hours; in the aggressive strategy, an additional 5000 U were given when vascular access was obtained or, if rescue PTCA was attempted, the dose increased to at least 2000-5000 U/hour. Prophylactic lidocaine, nitrates and angiotensin-converting enzyme inhibitors given as clinically indicated. Beta-blockers given only if indicated for hypertension, arrhythmia, or ischemia. Diltiazem, 30-60 mg tid throughout hospitalization

Principal Findings:

Combination thrombolytic therapy was associated with the following:
A less complicated clinical course, most clearly documented by a lower rate of reocclusion (2%) compared with urokinase (7%) and t-PA (12%) (p = 0.04)
A lower rate of recurrent ischemia (25%) compared with urokinase (35%) and t-PA (31%).
When a composite clinical end point (e.g., death, stroke, reinfarction, reocclusion, heart failure, or recurrent ischemia) was examined, combination thrombolytic therapy was associated with greater freedom from any adverse event (68%) compared with either single agent (urokinase, 55%; t-PA, 60%) (p = 0.04)
With a less complicated clinical course when the composite clinical end points were ranked according to clinical severity (p = 0.024). Early patency rates were greater with combination therapy, although predischarge patency rates after considering interventions to maintain patency were similar among drug regimens.
Compared with recombinant tissue-type plasminogen activator or urokinase monotherapy, combination therapy with these agents was associated with a lower need for acute intervention during the 1st 24 h after admission, but the difference did not reach statistical significance (14% for combination therapy vs. 21% for each agent alone, p = 0.30).

No difference in bleeding complication rates was observed with any thrombolytic regimen.

The aggressive catheterization strategy led to the following:
An overall early patency rate of 96% and a predischarge patency rate of 94% compared with a 90% predischarge patency in the conservative strategy (p = 0.065).
More patients treated with the aggressive strategy were free from adverse outcomes (67% vs. 55% in the conservative strategy, p = 0.004), and the clinical course was less complicated when the adverse outcomes were ranked according to severity (p = 0.016).
No significant increase in use of blood products resulted from the aggressive strategy.

Of 288 patients randomly assigned to a conservative postthrombolysis strategy, 54 (19%) required urgent cardiac catheterization within 24 h; 75 (26%) underwent urgent cardiac catheterization within 4 days of admission.

Of the clinical variables examined by multiple logistic regression analysis, only patient age and anterior wall myocardial infarction correlated with the need for urgent cardiac catheterization (p = 0.0016 and p = 0.017, respectively). Of the 75 patients undergoing urgent coronary angiography, only 39% had an occluded infarct-related artery. Emergency coronary angioplasty was performed in 49% of the patients and coronary artery bypass graft surgery was performed urgently in 3%. Despite these interventions, the need for urgent cardiac catheterization was associated with an in-hospital mortality rate of 7% (vs. 3% in the group not requiring urgent angiography, p = 0.36); mean left ventricular ejection fraction was 50.5 ±11% (vs. 54.3 ±10.8%, p = 0.12) and regional infarct zone wall motion was -2.68 ±1.07 SD/chord (vs. -2.46 ±1.19 SD/chord; p = 0.44).


These data suggest that a relatively large proportion of patients treated conservatively after thrombolytic therapy require early triage to urgent coronary angiography. Baseline clinical characteristics are poor predictors for urgent intervention. Despite ready access to facilities for aggressive intervention, the in-hospital clinical outcome of this group of conservatively treated patients appears to be poorer than that of patients without recurrent ischemia or hemodynamic instability.


1. Circulation 1991;83:1543-56. Final results
2. J Am Coll Cardiol 1991;18:1594-601. Determinants of early intervention
3. Am J Cardiol 1997;79(5):539-44. Predictors of LV function

Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, SCD/Ventricular Arrhythmias, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Lipid Metabolism, Novel Agents, Acute Heart Failure, Interventions and Imaging, Angiography, Nuclear Imaging, Hypertension

Keywords: Thrombolytic Therapy, Hospital Mortality, Urokinase-Type Plasminogen Activator, Ventricular Function, Left, Cardiac Catheterization, Cardiopulmonary Resuscitation, Drug Therapy, Combination, Electrocardiography, Fibrinolytic Agents, Anterior Wall Myocardial Infarction, Angioplasty, Balloon, Coronary, Triage, Shock, Cardiogenic, Coronary Angiography, Heart Failure, Stroke Volume, Coronary Artery Bypass, Tissue Plasminogen Activator, Hypertension, Logistic Models

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