Thrombolysis in Myocardial Infarction Trial, Phase 14 - TIMI 14


Abciximab with thrombolytic therapy for coronary patency in acute MI.


To assess the effect of combination abciximab and thrombolytic therapy on TIMI-3 flow at 90 minutes for patients with myocardial infarction.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 301 (Dose confirmation phase)
Mean Follow Up: 90 minutes (angiographic)
Female: 0

Patient Populations:

Between the ages of 18 and 75 years
Presented within 12 hours of ischemic symptoms lasting at least 30 minutes
At least 1 mm elevation of the ST segment


Prior coronary bypass surgery
Cardiogenic shock
Excess risk for bleeding
Thrombolytic therapy within the preceding 7 days

Primary Endpoints:

TIMI-3 flow at 60 and 90 minutes

Secondary Endpoints:

Major bleeding

Drug/Procedures Used:

The dose-finding phase of the study evaluated abciximab with t-PA, abciximab with streptokinase, and abciximab alone. Dose-confirmation phases assessed the effect of abciximab with 50mg t-PA combined with very-low-dose heparin regimens.

Concomitant Medications:

All patients received aspirin. All patients who received abciximab also received heparin.

Principal Findings:

Patients randomized to low-dose heparin with abciximab (either alone or with reduced-dose thrombolytic therapy) or standard-dose heparin (70 U/kg bolus followed by 15 U/kg/hr) with accelerated t-PA (up to 100mg). Patients who received abciximab (0.25 mg/kg bolus followed by 0.125 mcg/kg/min infusion for 12 hours) were further randomized to receive 1 of 12 thrombolytic doses, or no concomitant thrombolytic. Eight different t-PA regimens were tested, representing total doses of 20, 35, 50, and 65mg given as bolus, 30-, or 60- minute infusions. Four doses of streptokinase (500,000, 750,000, 1.25 million and 1.5 million units) were evaluated. A blinded core laboratory interpreted 90-minute angiograms for 98% of patients.

TIMI-3 flow at 90 minutes was achieved in 57% of patients given t-PA alone, compared to 32% of patients given abciximab alone. (For comparison, the TIMI-3 reperfusion rate was 30% for streptokinase alone in a meta-analysis of TIMI-1 and GUSTO-I results.)

Abciximab coupled with streptokinase produced TIMI-3 flow in 39-47% of patients. An arm combining abciximab with 1.5 million units of streptokinase arm was terminated early because of excess bleeding.

Abciximab therapy with t-PA produced TIMI-3 flow in 38-77% of patients. The most promising regimen used 50mg of t-PA: a 15mg t-PA bolus, followed by 35mg administered over 60 minutes.

Angiographic measurements of the speed and extent of thrombolysis were evaluated in terms of 60 and 90 minute TIMI-3 flow. The control (t-PA alone) arms had TIMI-3 flow in 45% of patients at 60 minutes and 57% of patients at 90 minutes, consistent with previous angiographic studies of t-PA. The best t-PA arm (bolus plus 60-minute infusion) had 65% TIMI-3 flow at 60 minutes (n=51) and 72% TIMI-3 flow at 90 minutes (n=101).

The rate of intracranial, retroperitoneal, or other major hemorrhage was 6% for the t-PA control, abciximab control, and pooled t-PA with abciximab arms. The major hemorrhage rate was 12% in the collective experience with streptokinase and abciximab.

In the dose-confirmation phase, the investigators examined the abciximab with 50mg t-PA regimen. Simultaneously, patients were randomized to low-dose heparin or very low-dose heparin (30 U/kg bolus with 4U/kg/hr infusion). TIMI-3 flow rates at 90 minutes were 63% for the control patients who received t-PA alone (n=208), compared to 77% for patients receiving abciximab with 50mg t-PA and low-dose heparin (n=93). The incidence of TIMI-3 flow was 68% for patients receiving abciximab, 50 mg t-PA, and very-low-dose heparin.


Combination abciximab and reduced-dose t-PA therapy appears to produce TIMI-3 flow in more patients than either agent alone. The 77% incidence of TIMI-3 flow rivals the reperfusion rate observed for primary angioplasty in GUSTO IIb (73%). Reperfusion may be faster for combination therapy, although the percentage of patients with TIMI-3 flow at 60 minutes may simply reflect the greater proportion of patients that do reperfuse at 90 minutes. The bleeding risk in the dose-ranging phase appears to be acceptable for the combination regimen selected for further study. Further trials must examine the effect of combination antiplatelet and thrombolytic therapy on clinical outcomes.


1. Presented at the XXth Congress of the European Society of Cardiology, Vienna, 1998

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

Keywords: Thrombolytic Therapy, Myocardial Infarction, Platelet Aggregation Inhibitors, Streptokinase, Heparin, Fibrinolytic Agents, Immunoglobulin Fab Fragments, Tissue Plasminogen Activator, Angioplasty

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