Late Assessment of Thrombolytic Efficacy Study - LATE
Late alteplase for mortality and cardiac rupture in acute MI.
rt-PA can reduce mortality even when used 12 hours after the onset of symptoms of an acute myocardial infarction (AMI).
Patients Screened: Not given
Patients Enrolled: 5,711
>18 years of age
Chest pain of suspected cardiac origin lasting >30 minutes
ECG exhibiting one or more of the following:
ST-segment elevation >0.1 mV in two or more limb leads or >0.2 mV in two or more chest leads.
ST-segment depression >0.2 mV in at least two leads and judged to represent a non-Q wave infarction
Patients with old or equivocal ECG changes or bundle branch block were considered for study entry in the presence of elevated serum cardiac enzyme levels.
Treatment could be initiated 6 to 24 hours after symptom onset.
Serious bleeding within the previous 6 months
Major surgery or trauma within the previous month
Shock with systolic blood pressure <80 mmHg
Hypertension (blood pressure > 200 mmHg systolic or 110 mmHg diastolic not controlled within the 6- to 24-hour time window
Inability to give informed consent or comply with the protocol
Death from cardiac rupture, electromechanical dissociation, asystole.
Severe bleeds requiring transfusion, death from other causes.
Alteplase, 10mg IV bolus, then 50 mg/hour over 1 hour and 20 mg/hour over 2 hours.
Immediate oral aspirin, then 75-300 mg/day. Heparin (recommended), initial IV bolus of 5000 U then either a further bolus of 5000 U and 1000 U/hour or 1000 U/hour
The LATE study provides clear evidence that the time window for thrombolysis with alteplase should be extended to 12 hours.
At a time in which little myocardial salvage can be expected, late thrombolysis (6 to 24 hours after the onset of symptoms associated with AMI) results in less signal-averaged ECG abnormality, principally in patients who present with ST-segment elevation on the ECG.
Intention-to-treat analysis of survival revealed a non-significant reduction in the alteplase group compared to placebo.
However, for treatment within 12 hours of onset of symptoms, there was a significant reduction of mortality at 35 days with alteplase. Relative reduction of mortality was 25.6% (p = 0.002). The difference for patients treated at 12-24 hours after symptom onset was less, though some patients may benefit even when treated after 12 hours.
Treatment with alteplase resulted in an excess of hemorrhagic strokes, but at 6 months, the number of disabled survivors was the same in both groups.
The risks of late thrombolysis appear very similar to those of early treatment.
For patients with clear indications for thrombolysis, the increased mortality from strokes is more than offset by a reduced mortality from other causes.
Cardiac rupture, electromechanical dissociation and asystole were no more common in the thrombolysis group, but they did manifest slightly earlier.
1. Lancet 1993;342:759-766. Final results
2. Circulation 1994;90:746-752. Signal-averaged EKG substudy
3. J Am Coll Cardiol 1995;25:1063-1068. Cardiac rupture
Keywords: Thrombolytic Therapy, Stroke, Chest Pain, Heart Rupture, Bundle-Branch Block, Heart Arrest, Electrocardiography, Tissue Plasminogen Activator
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