Lepirudin is a recombinant
hirudin derived from transfected yeast cells. The
hirudins are
direct thrombin inhibitors which render the
thrombin molecule incapable of promoting
fibrin formation and catalysing other haemostatic reactions. In initial studies, parenteral
lepirudin has shown promising efficacy as an
antithrombotic agent.
Lepirudin increased or maintained platelet counts at normal baseline values while maintaining adequate anticoagulation in patients with
heparin-induced
thrombocytopenia (HIT), and has not been associated with the development of immune-mediated
thrombocytopenia. Preliminary studies in patients with
deep vein thrombosis (DVT) suggest that
lepirudin may be more effective than
unfractionated heparin (UFH) at preventing pulmonary perfusion defects. In patients with
unstable angina pectoris, preliminary data also showed
lepirudin to be significantly more effective than UFH according to the combined incidence of cardiovascular mortality, new acute
myocardial infarction (AMI) or refractory angina. However, additional studies involving larger patient numbers are necessary before firm conclusions can be made regarding the relative efficacy of
lepirudin in these indications. Similarly, promising but limited data on the use of
lepirudin during haemodialysis or heart surgery and in patients with
disseminated intravascular coagulation (
DIC) require further confirmation.
Bleeding complications and the possible induction of allergic or
anaphylactic reactions are the most serious adverse events associated with
lepirudin therapy. Major
bleeding complication rates appear to be similar with
lepirudin and UFH monotherapy; however,
lepirudin may be associated with an increased incidence of minor
bleeding including bruising. Initial encouraging results showing an improvement in coronary artery patency with high-dose
lepirudin versus UFH as an adjunct to
thrombolytic therapy in patients with AMI were subsequently overshadowed by reports of a high incidence of major
bleeding events including cerebral haemorrhage among
lepirudin recipients. Moreover, at lower doses which did not produce an unacceptably high incidence of haemorrhagic complications,
lepirudin appeared to have only a small efficacy advantage over UFH.
CONCLUSIONS:
Lepirudin has shown promising activity as an
antithrombotic agent and may be a suitable substitute
anticoagulant for
heparin in patients with HIT. The narrow therapeutic window of
lepirudin makes it difficult to assess the role of this agent when used as an adjunct to
thrombolytic therapy in patients with AMI. However, initial data suggest that
lepirudin may be a potentially useful agent in the management of patients with
unstable angina, DVT or
DIC and in preventing
thrombus formation in extracorporeal circuits. Further studies should more fully elucidate the efficacy of
lepirudin in these indications.