, Volume 65, Issue 13, pp 1869–1891 | Cite as


A Review of its Use in Patients Undergoing Percutaneous Coronary Intervention
  • Marit D. Moen
  • Gillian M. Keating
  • Keri Wellington
Adis Drug Evaluation



Bivalirudin (Angiox™, Angiomax®) is a synthetic 20-amino acid peptide analogue of hirudin. It is a direct thrombin inhibitor that binds specifically and reversibly to both fibrin-bound and unbound thrombin. Intravenous bivalirudin is approved in Europe for use as an anticoagulant in patients undergoing percutaneous coronary intervention (PCI). In the US, bivalirudin is approved in patients with unstable angina pectoris undergoing percutaneous transluminal coronary angioplasty (PTCA) and has recently been approved for use with provisional glycoprotein (GP) IIb/IIIa inhibition in patients undergoing PCI.

Bivalirudin plus provisional GP IIb/IIIa inhibition is effective in patients undergoing PCI. The large, well controlled REPLACE-2 (Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events) study showed that bivalirudin plus provisional GP IIb/IIIa inhibition was noninferior to heparin plus planned GP IIb/IIIa inhibition and that bivalirudin was associated with a reduced risk of bleeding complications. In patients with heparin-induced thrombocytopenia (HIT), bivalirudin was effective against ischaemic events and there was a low incidence of bleeding complications. Bivalirudin should be considered as an alternative to heparin plus planned GP IIb/IIIa inhibition in any patient undergoing urgent or elective PCI, especially in any patient with a high risk of bleeding complications.

Pharmacological Properties

Bivalirudin directly inhibits thrombin by binding to the active site and exosite 1 of thrombin. This binding is specific, noncompetitive and initially irreversible. The inhibition is reversed as bivalirudin is slowly cleaved by thrombin, freeing the active site and allowing thrombin to regain its activity.

Intravenous administration of bivalirudin results in a dose-dependent increase in anticoagulation parameters. Bivalirudin inhibits thrombin generation and activity, as well as thrombin-mediated platelet activation.

Bivalirudin does not bind to plasma proteins other than thrombin and has a small volume of distribution. It is cleared from plasma by a combination of proteolytic cleavage and renal mechanisms; bivalirudin plasma clearance is affected by impaired renal function. In patients with normal renal function, bivalirudin is rapidly cleared from plasma and has a terminal half-life of 25 minutes.

Therapeutic Efficacy

The REPLACE-2 trial in patients undergoing PCI found that bivalirudin plus provisional GP IIb/IIIa inhibition was noninferior to heparin plus planned GP IIb/IIIa inhibition for the composite primary endpoint of death, myocardial infarction (MI), repeat revascularisation or major bleeding at 30 days, or for the secondary endpoint of death, MI or repeat revascularisation. There was no between-group difference in the incidence of all-cause mortality after 1 year.

Similar outcomes were observed in REPLACE-2 substudies of special patient groups, including patients with impaired renal function, diabetes mellitus or acute coronary syndromes, and in other studies in patients undergoing brachytherapy or patients with HIT.


Bivalirudin has been associated with a lower incidence of bleeding complications than heparin. In the REPLACE-2 trial, there was a significant 41% relative reduction in the incidence of major bleeding in the bivalirudin plus provisional GP IIb/IIIa inhibitor group compared with the heparin plus planned GP IIb/IIIa inhibitor group (2.4% vs 4.1%; p < 0.001).

The incidence of major bleeding was lower in bivalirudin recipients than heparin recipients across most analysed subgroups of patients including those with impaired renal function or anaemia and female patients. The incidence of bleeding events was also low in a noncomparative trial of bivalirudin in patients with HIT.

Bivalirudin was generally well tolerated. In REPLACE-2, the most frequent adverse events in bivalirudin recipients were back pain, angina pectoris, pain, hypotension and nausea.

Pharmacoeconomic Considerations

Total 30-day costs were lower for bivalirudin plus provisional GP IIb/IIIa inhibitor recipients than for heparin plus planned GP IIb/IIIa inhibitor recipients ($US10 868 vs $US11 242; year of costing 2002) in REPLACE-2. Approximately 80% of the cost reduction was due to a difference in anticoagulation cost (between bivalirudin and GP IIb/IIIa inhibitors) and 20% was due to differences in the incidences of ischaemic and haemorrhagic complications.


Percutaneous Coronary Intervention Major Bleeding Abciximab Bivalirudin Activate Clotting Time 
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Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Marit D. Moen
    • 1
  • Gillian M. Keating
    • 1
  • Keri Wellington
    • 1
  1. 1.Adis International LimitedMairangi Bay, AucklandNew Zealand

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