Hirudin for the Improvement of Thrombolysis - HIT-I
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.
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.
Patients Enrolled: 40
Mean Follow Up: Hospital discharge
Mean Patient Age: 25-75
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.
Contraindication to thrombolysis or renal failure
Rates of TIMI 2 or 3 flow, and rates of reocclusion during hirudin infusion
Time to reperfusion, patency rate of infarct-related vessel at 90 minutes, and bleeding complications
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.
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.
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.
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.
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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