Document Detail

HBW 023 (recombinant hirudin) for the acceleration of thrombolysis and prevention of coronary reocclusion in acute myocardial infarction: results of a dose-finding study (HIT-II) by the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte.
MedLine Citation:
PMID:  9710686     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To define an optimal dose of hirudin that would improve early coronary artery Thrombolysis in Myocardial Infarction grade 3 (TIMI 3) patency and prevent reocclusions in patients with acute myocardial infarction treated with front-loaded recombinant tissue-type plasminogen activator (rt-PA). METHODS: Recombinant hirudin (HBW 023) was tested in a sequential dose-escalating study as adjunct to front-loaded rt-PA in 143 patients with acute myocardial infarction. The sequential model was assigned two 'decision boundaries': it triggered an increase in dosage if the 60-min TIMI 3 flow rate in a dosage group was statistically not consistent with a target patency rate of 75%, or if the deterioration in coronary blood flow (of at least one TIMI grade, from TIMI 2 or 3, from one angiography to the next) exceeded 5%. RESULTS: The decision boundary for TIMI 3 flow grade at 60 min was crossed when 18 patients were treated with 0.1/0.06 mg/kg (bolus/infusion per hour over 48 h) r-hirudin (dosage group I), 42 patients treated with 0.2/0.1 mg/kg (dosage group II), and 83 patients with 0.4/0.15 mg/kg (dosage group III). TIMI 3 flow at 60 min was 50%, 58%, and 63% in dosage groups I-III, respectively (P = 0.15). Early, complete, and sustained patency (TIMI 3 flow at 60 min, 90 min and 48 h) were 44%, 55% and 64% (P = 0.07). Reocclusion between 90-min and 48-h angiograms or reinfarction occurred in 0 to 15, two of 36, and one of 72 patients, respectively (P = 0.5). Four patients (2.8%) died in hospital and 14 patients suffered a major bleeding event, but no intracranial bleeding was encountered. CONCLUSIONS: With increasing doses of hirudin, there was a trend towards greater early and complete patency, but no clear dose--response relationship was observed. A borderline significant effect was observed with respect to early, complete, and sustained patencies. In all groups, reocclusions or reinfarctions were rare. Neither clinical nor laboratory data predicted the imbalance in haemorrhagic events observed in a subsequent, prematurely terminated, phase III trial with hirudin and rt-PA.
R von Essen; U Zeymer; U Tebbe; A Jessel; H Kwasny; M Mateblowski; W Niederer; J Wagner; W Mäurer; E R von Leitner; K Haerten; M Roth; K L Neuhaus
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Publication Detail:
Type:  Clinical Trial; Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Coronary artery disease     Volume:  9     ISSN:  0954-6928     ISO Abbreviation:  Coron. Artery Dis.     Publication Date:  1998  
Date Detail:
Created Date:  1998-10-20     Completed Date:  1998-10-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9011445     Medline TA:  Coron Artery Dis     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  265-72     Citation Subset:  IM    
Medical Clinic, Stiftsklinikum Augustinum München, Germany.
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MeSH Terms
Coronary Angiography
Fibrinolytic Agents / administration & dosage*
Hirudins / administration & dosage,  analogs & derivatives*
Middle Aged
Myocardial Infarction / drug therapy*,  radiography
Myocardial Reperfusion
Recombinant Proteins / administration & dosage
Thrombolytic Therapy*
Time Factors
Tissue Plasminogen Activator / therapeutic use
Vascular Patency
Reg. No./Substance:
0/Fibrinolytic Agents; 0/Hirudins; 0/Recombinant Proteins; 0/lepirudin; EC Plasminogen Activator

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