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Hirudin for the Improvement of Thrombolysis - HIT-I
Description:
HIT-I was a pilot study to determine the feasibility, efficacy, and safety of recombinant hirudin as adjunctive therapy to thrombolysis with t-PA in patients with ST elevation myocardial infarction.
Hypothesis:
Recombinant hirudin given as adjunctive therapy to thrombolysis with t-PA is safe. In animal models, this therapy was shown to accelerate thrombolysis and reduce reocclusions.
Study Design
Study Design:
Patients Enrolled: 40
Mean Follow Up: Hospital discharge
Mean Patient Age: 25-75
Female: 20
Patient Populations:
Men and women aged 25 to 75 with onset of typical ischemic chest pain <6 hours. ECG with ST elevation >2 mm in at least two precordial leads or >1 mm in two frontal leads.
Exclusions:
Contraindication to thrombolysis or renal failure
Primary Endpoints:
Rates of TIMI 2 or 3 flow, and rates of reocclusion during hirudin infusion
Secondary Endpoints:
Time to reperfusion, patency rate of infarct-related vessel at 90 minutes, and bleeding complications
Drug/Procedures Used:
Patients received a bolus of hirudin (0.07 mg/kg) followed by an infusion (0.05 mg/kg/h) for 48 hours. Thrombolysis was with t-PA (Actilyse) 15 mg bolus followed by a 50 mg infusion over 30 minutes and a 35 mg infusion over 60 minutes. All patients underwent angiography at 30, 60, and 90 minutes after the start of thrombolytic therapy and again at 24-48 hours.
Concomitant Medications:
Aspirin and heparin were prohibited during the hirudin infusion for safety reasons. After completion of hirudin treatment, aspirin or heparin was given at the discretion of the physician.
Principal Findings:
Forty patients were enrolled. Eighty percent were men and average age was 59 years. Forty-five percent had anterior myocardial infarctions. Median time from symptom onset to hirudin infusion was 3.2 hours.
Rates of TIMI 2 or 3 flow were as follows: 51.3% at 30 minutes, 84.6% at 60 minutes, 92% at 90 minutes, and 85% at 24 to 48 hours. In 37 of the 40 patients, the infarct-related artery was patent at 90 minutes. In 6 of the 37 patent arteries, reocclusion was angiographically documented during the hirudin treatment phase (at 24-48 hours). No reocclusions occurred between the 48-hour angiogram and discharge. Major bleeding was observed in three patients.
Interpretation:
This small pilot study shows that hirudin as adjunctive therapy to thrombolysis was generally safe and effective. However, the high rate of reocclusions indicate the need for further dose-finding investigations. The subsequent HIT-II trial investigated the dose-response relationship of hirudin to patency and reocclusions.
References:
Zeymer U, von Essen R, Tebbe U, et al. Recombinant hirudin and front-loaded alteplase in acute myocardial infarction: final results of a pilot study. HIT-I (hirudin for the improvement of thrombolysis). Eur Heart J 1995;16 Suppl D:22-7.
Keywords: Hirudin Therapy, Thrombolytic Therapy, Myocardial Infarction, Chest Pain, Recombinant Proteins, Electrocardiography, Tissue Plasminogen Activator, Hirudins
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