Sm. Bates et Ji. Weitz, DIRECT THROMBIN INHIBITORS FOR TREATMENT OF ARTERIAL THROMBOSIS - POTENTIAL DIFFERENCES BETWEEN BIVALIRUDIN AND HIRUDIN, The American journal of cardiology, 82, 1998, pp. 12-18
Given the central role of thrombin in arterial thrombogenesis, most tr
eatment strategies for acute coronary syndromes are aimed at inhibitin
g its generation or blocking its activity. Although heparin has been w
idely used, it has limitations in the setting of arterial thrombosis.
These limitations reflect the inability of heparin to inactivate throm
bin bound to fibrin, a major stimulus for thrombus growth. In addition
, the anticoagulant response to heparin varies from patient to patient
, and heparin is neutralized by platelet Factor IV, large quantities o
f which are released from platelets activated at sites of plaque ruptu
re. Consequently, heparin requires careful laboratory monitoring to en
sure an adequate anticoagulant effect. Direct thrombin inhibitors, suc
h as hirudin and bivalirudin, overcome the limitations of heparin. The
se agents inhibit fibrin-bound thrombin, as well as fluid-phase thromb
in, and produce a predictable anticoagulant response. Bivalirudin has
both safety and potential efficacy advantages over hirudin. Bivalirudi
n appears to have a wider therapeutic window than hirudin, possibly be
cause bivalirudin only transiently inhibits the active site of thrombi
n. The better safety profile of bivalirudin permits administration of
higher doses, which may give it an efficacy advantage. Hirudin prevent
s thrombin from activating protein C, thereby suppressing this natural
anticoagulant pathway. In contrast, bivalirudin may promote protein C
activation by transiently inhibiting thrombin until it can be bound b
y thrombomodulin. Differences between bivalirudin and hirudin, as well
as other direct thrombin inhibitors, highlight the pitfalls of consid
ering all direct thrombin inhibitors to hove equivalent risk-benefit p
rofiles. (C) 1998 by Excerpta Medica, Inc.