Hirulog Early Reperfusion/Occlusion Trial - HERO


The HERO trial was designed to compare the efficacy and safety of low or high dose hirulog, a direct thrombin inhibitor, vs heparin for achieving early and complete flow of the infarct related artery in acute MI patients receiving streptokinase and aspirin.


TIMI 3 flow at 90 to 120 minutes would improve from 30% with heparin to 46% with the combination of the two hirulog regimens (1:2 comparison) or to 48% with one of the hirulog regimens (1:1 comparison).

Study Design

Study Design:

Patients Enrolled: 412
Mean Follow Up: 35 days
Mean Patient Age: not reported
Female: 25
Mean Ejection Fraction: The ejection fraction at day 2-3 was as follows: heparin, 60.7±1.3; low dose hirulog, 58.1±1.4; high-dose hirulog 60.7±1.3 (p=0.11 for heparin vs all hirulog patients).

Patient Populations:

Presentation within 12 hours of the onset of symptoms. Infarction with 1 mm of ST-segment elevation in 2 limb leads and/or leads V4 through V6 of a 12-lead ECG or 2 mm of ST-segment elevation in 2 contiguous precordial V1 through V3 leads.


Previous administration of streptokinase. History of systemic, gastrointestinal, or genitourinary bleeding within 3 months. History of cerebrovascular disease including stroke or transient ischemic attack within 6 months. History of intracranial neoplasm, arteriovenous malformation, or aneurysm. Severe trauma or major surgery within the previous 3 months. Puncture of noncompressible vessels within the previous 10 days. Traumatic cardiopulmonary resuscitation within the previous month. Severe and uncontrolled hypertension. Cardiogenic shock.

Primary Endpoints:

Complete patency (TIMI grade 3 flow) at 90-120 minutes.

Secondary Endpoints:

Complete patency (TIMI grade 3 flow) at 2-3 days. Left ventricular function, global ejection fraction, end-systolic volume, and regional wall motion at 2 to 3 days in patients without a prior history of myocardial infarction. Incidence of death, stroke, reinfarction and cardiogenic shock at 35 days after treatment.

Drug/Procedures Used:

Patients received 150-325 mg aspirin after admission and continued daily thereafter. Streptokinase (1.5 million U) was administered over 30-60 minutes. Patients were randomized to either heparin (5000 U bolus + infusion of 1000 U/h for those <80 kgs and 1200 U/h for those >=80 kg for up to 60 hours); or low dose hirulog (0.125 mg/kg IV bolus + infusion of 0.25 mg/kg/h for 12 hours followed by 0.125 mg/kg/h for up to 60 hours); or high dose hirulog (0.25 mg/kg IV bolus + infusion of 0.5 mg/kg/h for 12 hours followed by 0.25 mg/kg/h for up to 60 hours). Patients underwent angiography at 90-120 minutes and again at 2-3 days after thrombolytic administration.

Principal Findings:

TIMI 3 flow was lower with heparin than with hirulog (35% with heparin, 46% with low-dose hirulog, and 48% with high-dose hirulog; heparin vs hirulog, p=0.024; heparin vs high-dose hirulog, p=0.03). Reocclusion (TIMI 2 or 3 flow reducing to TIMI 0 or 1 flow) had occurred by the 2/3 day angiogram in 7% of heparin, 4.6% of low-dose hirulog, and 1.3% of high-dose hirulog patients (p=NS). By day 35, the composite of death, cardiogenic shock, or reinfarction had occurred in 17.9% of heparin patients, 14% of low-dose hirulog patients, and 12.5% of high-dose hirulog patients (p=NS). Two strokes occurred in both the heparin and high-dose hirulog arms, but none in the low-dose hirulog arm. Major bleeding occurred in 28% of heparin, 14% of low-dose hirulog, and 19% of high-dose hirulog patients (heparin vs low-dose hirulog, p<0.01).


The direct thrombin inhibitor hirulog was more effective than heparin in producing early and complete patency in acute MI as an adjunct to streptokinase and aspirin without increasing the risk of major bleeding. The effect hirulog may be dose dependent. A large randomized follow-up trial, HERO-2, was subsequently designed to test the clinical efficacy of hirulog compared with heparin as an adjunct to streptokinase.


Circulation. 1997;96:2155-2161.

Clinical Topics: Anticoagulation Management, Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Hirudin Therapy, Stroke, Myocardial Infarction, Follow-Up Studies, Platelet Aggregation Inhibitors, Heparin, Electrocardiography, Shock, Cardiogenic, Streptokinase, Recombinant Proteins, Peptide Fragments

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