Accelerated Plasminogen Activator Dose Regimens for Coronary Thrombolysis - TAMI-7

Description:

TAMI-7 was a parallel-group, dose-ranging trial designed to evaluate safety and efficacy of several dose regimens of r-PA in fibrinolysis of acute ST elevation myocardial infarction (STEMI).

Hypothesis:

Acelerated r-PA therapy for acute MI will be associated with a higher coronary artery patency during initial and follow-up coronary angiography, compared with expected patency rates of standard dosing regimen.

Study Design

Study Design:

Patients Screened: 232
Patients Enrolled: 232
Mean Follow Up: 5-10 days following fibrinolysis
Mean Patient Age: Average age 55-60 years
Mean Ejection Fraction: At follow-up, median (25th/50th/75th percentile):
Group A: 48/56/64
Group B: 48/57/64
Group C: 47/53/60
Group D: 39/51/57
Group E: 44/54/61

Patient Populations:

Age >18 and <76 years, symptoms consistent with acute MI of >30 minutes' duration, and onset of symptoms not more than six hours prior to administration of fibrinolysis

Exclusions:

Contraindication(s) to fibrinolysis, prior coronary artery bypass grafting, or prior MI in the same coronary artery distribution

Primary Endpoints:

Infarct-related patency rates during acute coronary angiography, and reocclusion rates during follow-up coronary angiography

Secondary Endpoints:

Bleeding complications, left ventricular function, recurrent ischemia, and congestive heart failure

Drug/Procedures Used:

Patients were enrolled within six hours of onset of symptoms of STEMI, and were administered r-PA within one of the five dosing regimens: group A—1 mg/kg over 30 minutes, then 0.25 mg/kg over 30 minutes (10% bolus); group B—1.25 mg/kg over 90 minutes (20 mg bolus); group C—0.75 mg/kg over 30 minutes, then 0.5 mg/kg over 60 minutes (10% bolus); group D—20 mg bolus, then 30-minute wait, then 80 mg over 120 minutes; group E—1 mg/kg over 30 minutes + urokinase (1.5 million U) over 60 minutes.

All patients subsequently underwent emergency coronary angiography ≥90 minutes following fibrinolysis, at which time the infarct-related artery (IRA) patency was assessed. IRA was identified as patent if TIMI grade 2 or 3 flow was present at the time of the fourth injection. IRA with TIMI 0 or 1 flow was defined as occluded. Subsequently, a follow-up coronary angiography was performed 5-10 days after fibrinolysis. Left ventriculography was performed at the time of both acute and follow-up catheterization. Aspirin and intravenous unfractionated heparin were administered following fibrinolysis.

Concomitant Medications:

Aspirin 325 mg/day, and heparin IV 1000 U/h

Principal Findings:

A total of 232 patients were enrolled in the study. Of those, three patients received no fibrinolysis, nine were misdiagnosed as having acute STEMI, and one patient received a fibrinolytic regimen different from that specified in the trial. Therefore, data from 219 patients were included in the analysis.

Patency rates were: group A—63%; group B—61%; group C—83%; group D—72%; group E—77%. Reocclusion rates were: group A—11%; group B—3%; group C—4%; group D—3%; and group E—13.6%. Death, reocclusion, restenosis, and reinfarction tended to be less frequent with regimen C. There were no significant differences in the incidence of recurrent ischemia or congestive heart failure among the different treatment strategies.

Global ejection fraction and regional wall function showed a marginal improvement with all treatment strategies.

Median change in hematocrit was not different among the five treatment groups, and no clinically-significant difference in moderate to severe bleeding was seen.

Interpretation:

This study shows that whereas the bleeding complications appear to be similar to those in older reports using conventional r-PA dosing, a more accelerated infusion of r-PA was not associated with a higher infarct-related patency rate than conventional dosing among patients with STEMI. Interestingly, the most accelerated regimen (those without a significant front-loaded 30-minute infusion) was associated with lower coronary patency rates. The authors explained this by proposing that plasminogen receptors are quickly saturated, and fibrinolysis is thus less efficient.

References:

Wall TC, Califf RM, George BS, et al. Accelerated plasminogen activator dose regimens for coronary thrombolysis. The TAMI-7 Study Group. J Am Coll Cardiol 1992;19:482-9.

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

Keywords: Thrombolytic Therapy, Myocardial Infarction, Follow-Up Studies, Urokinase-Type Plasminogen Activator, Heparin, Fibrinolytic Agents, Hematocrit, Coronary Angiography, Plasminogen, Fibrinolysis, Heart Failure, Catheterization, Recombinant Proteins, Tissue Plasminogen Activator


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