A Multicenter, Randomized Study of Argatroban Versus Heparin as Adjunct to Tissue Plasminogen Activator (TPA) in Acute Myocardial Infarction: Myocardial Infarction With Novastan and TPA (MINT) Study - MINT

Description:

The goal of this study was to assess the angiographic and clinical outcomes following either argatroban or heparin-enhanced tissue plasminogen activator (TPA) among patients with ST-segment elevation myocardial infarction (MI).

Hypothesis:

Direct thrombin inhibitors, such as argatroban, may enhance reperfusion with TPA in patients with acute MI.

Study Design

Study Design:

Patients Enrolled: 125
Mean Follow Up: 30 days

Patient Populations:

  • Men or nonpregnant women
  • Ischemic chest discomfort lasting at least 30 minutes
  • ST-segment elevation of ≥0.2 mV in at least two contiguous precordial leads or ≥0.1 mV in at least two limb leads
  • Time from presentation to therapy <6 hours

Exclusions:

  • History of stroke, hemodynamic instability, recent angioplasty, or coronary bypass surgery
  • Patients already receiving heparin

Primary Endpoints:

  • Percentage of patients with TIMI grade 3 flow
  • Composite of death, recurrent MI, percutaneous transluminal coronary angioplasty, coronary artery bypass surgery, shock/new-onset congestive heart failure, and recurrent ischemia at 30 days

Secondary Endpoints:

Mean corrected TIMI frame count at 90 minutes

Drug/Procedures Used:

Patients were randomized to one of three arms:
  • Heparin 70 U/kg and 15 U/kg/h
  • Argatroban 100 µg/kg and 1.0 µg/kg/min
  • Argatroban 100 µg/kg and 3.0 µg/kg/min
(Study drug and TPA were given within five minutes of each other.)

Concomitant Medications:

  • TPA 15 mg bolus, followed by 0.75 mg/kg (up to 50 mg) over 30 minutes, followed by 0.5 mg/kg (up to 35 mg) over the next 60 minutes
  • Aspirin 160-325 mg one hour prior to TPA

Principal Findings:

    At 90 minutes:
  • TIMI grade 3 flow was not statistically different among the three groups (p=0.20 vs. heparin).
  • Corrected TIMI frame count was not statistically different among the three groups (0.74 vs. heparin).
  • At 3-6 hours:

  • TIMI grade 3 flow was achieved in 20.0%, 50.0%, and 57.1% of the heparin, low-dose argatroban, and high-dose argatroban groups, respectively (p=0.03 vs. heparin).
  • Corrected TIMI frame count was 54.4 ± 9.7, 32.9 ± 4.9, and 26.6 ± 3.2 in the heparin, low-dose argatroban and high-dose argatroban groups, respectively (p=0.01 vs. heparin).
  • Complications:

  • Major bleeding in 10.0%, 2.6%, and 4.3% of heparin, low-dose argatroban, and high-dose argatroban groups, respectively (p=0.29 vs. heparin).
  • Although not powered sufficiently, the composite endpoint of death, recurrent MI, shock/heart failure, revascularization, and recurrent ischemia at 30 days occurred in 37.5%, 31.6%, and 25.5% of the heparin, low-dose, and high-dose argatroban groups, respectively (p=0.23).

Interpretation:

Among patients with ST-segment elevation MI, enhancing the fibrinolytic effects of TPA with high-dose argatroban (compared with heparin) is associated with an increased rate of TIMI grade 3 flow at 3-6 hours after the onset of symptoms. The study was not powered to adequately detect clinical differences among the three groups. The rate of major bleeding was not statistically different among the three groups.

References:

Jang IK, Brown DF, Giugliano RP, et al. A multicenter, randomized study of argatroban versus heparin as adjunct to tissue plasminogen activator (TPA) in acute myocardial infarction: myocardial infarction with novastan and TPA (MINT) study. J Am Coll Cardiol 1999;33:1879-85.

Clinical Topics: Anticoagulation Management, Dyslipidemia, Heart Failure and Cardiomyopathies, Lipid Metabolism, Novel Agents, Acute Heart Failure

Keywords: Pipecolic Acids, Thrombolytic Therapy, Myocardial Infarction, Thrombin, Platelet Aggregation Inhibitors, Pyridinolcarbamate, Heart Failure, Heparin, Fibrinolytic Agents, Tissue Plasminogen Activator


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