PMID- 11833835
OWN - NLM
STAT- MEDLINE
DCOM- 20020710
LR  - 20220318
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 24
IP  - 1
DP  - 2002 Jan
TI  - Bivalirudin: a direct thrombin inhibitor.
PG  - 38-58
AB  - BACKGROUND: Studies of the anticoagulant effects of hirudin, which is derived 
      from the saliva of the leech Hirudo medicinalis, led to the development of 
      compounds that can directly inhibit thrombin activity without the need for 
      additional cofactors. One of these is the direct thrombin inhibitor bivalirudin, 
      which has recently been approved by the US Food and Drug Administration for use 
      as an anticoagulant in patients with unstable angina undergoing percutaneous 
      transluminal coronary angioplasty. OBJECTIVE: This is a review of the 
      pharmacologic properties, efficacy, tolerability, and potential 
      cost-effectiveness of bivalirudin in the treatment of ischemic coronary 
      syndromes. METHODS: Articles were identified by searches of MEDLINE 
      (1966-September 2001), International Pharmaceutical Abstracts (1970-September 
      2001), and the Iowa Drug Information Service (1966-September 2001) using the 
      terms bivalirudin and Hirulog. The reference lists of retrieved articles were 
      also reviewed for relevant articles. RESULTS: Bivalirudin is a synthetic 
      polypeptide that directly inhibits thrombin by binding simultaneously to its 
      active catalytic site and its substrate recognition site. After intravenous 
      administration, peak plasma concentrations occur in 2 minutes. In patients given 
      a 1.0-mg/kg bolus followed by a 2.5-mg/kg per hour infusion, a median activated 
      clotting time of 346 seconds is achieved with little interpatient or intrapatient 
      variability. Clearance of bivalirudin occurs through a combination of renal 
      elimination and proteolytic cleavage, and doses may need to be decreased in the 
      presence of renal dysfunction. In patients undergoing percutaneous coronary 
      interventions, bivalirudin has been associated with equivalent efficacy but lower 
      bleeding rates (P < 0.001) than unfractionated heparin (UFH). Data from the 
      Hirulog Early Reperfusion/Occlusion-2 study suggest no reduction in mortality 
      with bivalirudin compared with heparin when either is added to aspirin and 
      streptokinase in patients with acute myocardial infarction, despite a lower 
      reinfarction rate (P < 0.001). Experience with bivalirudin in patients with 
      unstable angina and heparin-induced thrombocytopenia (HIT), as well as in 
      patients receiving glycoprotein IIb/IIIla inhibitors, is limited. The differences 
      in bleeding rates between bivalirudin and heparin in published clinical trials 
      probably reflect differences in levels of anticoagulation achieved in comparator 
      groups. CONCLUSIONS: Given its high cost, bivalirudin should be reserved for use 
      as an alternative to UFH, primarily in patients with HIT, until clinical trials 
      have more clearly demonstrated its benefits in terms of efficacy or safety.
FAU - Gladwell, Timothy D
AU  - Gladwell TD
AD  - Duquesne University School of Pharmacy, Pittsburgh, Pennsylvania 15282, USA. 
      gladwell@duq.edu
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Anticoagulants)
RN  - 0 (Antithrombins)
RN  - 0 (Hirudins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Recombinant Proteins)
RN  - TN9BEX005G (bivalirudin)
SB  - IM
MH  - Angina, Unstable/drug therapy
MH  - Angioplasty, Balloon, Coronary
MH  - Anticoagulants/adverse 
      effects/economics/pharmacokinetics/pharmacology/*therapeutic use
MH  - Antithrombins/adverse effects/pharmacokinetics/pharmacology/*therapeutic use
MH  - Clinical Trials as Topic
MH  - *Hirudin Therapy
MH  - Hirudins/adverse effects/*analogs & 
      derivatives/economics/pharmacokinetics/pharmacology
MH  - Humans
MH  - Myocardial Infarction/drug therapy
MH  - Peptide Fragments/adverse 
      effects/economics/pharmacokinetics/pharmacology/*therapeutic use
MH  - Recombinant Proteins/adverse 
      effects/economics/pharmacokinetics/pharmacology/*therapeutic use
MH  - Thrombocytopenia/drug therapy
MH  - Thrombosis/blood/economics/*prevention & control
RF  - 45
EDAT- 2002/02/09 10:00
MHDA- 2002/07/12 10:01
CRDT- 2002/02/09 10:00
PHST- 2002/02/09 10:00 [pubmed]
PHST- 2002/07/12 10:01 [medline]
PHST- 2002/02/09 10:00 [entrez]
AID - S0149-2918(02)85004-4 [pii]
AID - 10.1016/s0149-2918(02)85004-4 [doi]
PST - ppublish
SO  - Clin Ther. 2002 Jan;24(1):38-58. doi: 10.1016/s0149-2918(02)85004-4.