Bivalirudin

Overview

Thrombin is the central enzyme of the coagulation cascade, converting fibrinogen to fibrin and activating platelets. Bivalirudin is a bivalent, directly acting inhibitor: one end binds thrombin's catalytic site while the other binds its fibrinogen-recognition exosite, blocking both free and clot-bound thrombin. Unlike heparin, it does not require antithrombin and is not inactivated by platelet factor 4.

In the HORIZONS-AMI trial, bivalirudin monotherapy during primary PCI for ST-elevation myocardial infarction reduced major bleeding and mortality compared with heparin plus a glycoprotein IIb/IIIa inhibitor, and this benefit persisted at 3 years.

Bivalirudin has predictable, linear pharmacokinetics and a short half-life (~25 minutes), being cleared partly by proteolysis and partly renally, so its effect wanes quickly after the infusion stops. Its main risk, as with all anticoagulants, is bleeding; dose is reduced in significant renal impairment.

Mechanism of Action

Its N-terminal D-Phe-Pro-Arg-Pro segment occupies the catalytic cleft while a glycine-linked C-terminal sequence engages exosite I. Binding is reversible: thrombin slowly cleaves the Arg-Pro bond, restoring enzyme activity, which contributes to the drug's short duration of action. Independence from antithrombin gives a more predictable anticoagulant response than heparin.

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