Summary
Bivalirudin is a direct thrombin inhibitor (DTI) frequently used for anticoagulation
in the setting of invasive cardiology, particularly percutaneous coronary intervention
(PCI). Bivalirudin has a unique pharmacologic profile: unlike other marketed DTIs,
it undergoes predominant non-organ elimination (proteolysis), and has the shortest
half-life (~25 min). Its affinity for thrombin is intermediate between that of lepirudin
(highest) and argatroban (lowest) — this helps explain why it interferes with functional
clotting assays to an extent intermediate between that achieved by these two other
DTIs. This effect is best known for the PT (INR) — higher affinity for thrombin corresponds
to lower molar DTI requirements to prolong the APTT; in turn, lower concentrations
required for APTT prolongation (and, presumably, in-vivo effect) result in reduced
PT (INR) prolongation. Bivalirudin is primarily used for its first FDA-approved indication,
namely anticoagulation during percutaneous transluminal coronary angioplasty ("balloon
angioplasty"), the most frequent type of PCI. Bivalirudin is also indicated for PCI
with provisional use of glycoprotein IIb/IIIa antagonist therapy, and for patients
with, or at risk of, heparin-induced thrombocytopenia (HIT), or HIT with thrombosis
syndrome (HITTS), undergoing PCI. The bivalirudin development program has used a "quadruple"
endpoint comprising a "triple" efficacy endpoint plus major bleeding —this approach
anticipated the subsequent emphasis on strategies to improve clinical outcomes through
bleeding reduction. Besides summarizing the key trials evaluating bivalirudin use
for acute coronary syndrome (especially employing PCI), we review also the studies
of bivalirudin as anticoagulant for "on-" and "off-pump" cardiac surgery, including
both HIT and non-HIT situations.
Keywords Bivalirudin - direct antithrombin agents - direct thrombin inhibitors
