Desirudin, a recombinant
hirudin used in the prevention and management of thromboembolic disease, is a
thrombin inhibitor which binds directly and with high affinity to clot-bound and fluid phase
thrombin. As a prophylaxis in patients undergoing hip replacement surgery,
desirudin was significantly more effective in reducing the incidence of
deep vein thrombosis (DVT) than either unfractionated or
low molecular weight heparin. However, results in patients with
acute coronary syndromes are less conclusive. A significant reduction with
desirudin compared with
heparin in the incidence of death or non-fatal (re)
infarction at 24 hours in patients with acute
myocardial infarction (MI) was reported in the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) IIb trial but not in the TIMI (Thrombolysis and
Thrombin Inhibition in
Myocardial Infarction) 9B trial. Despite the early reduction shown in GUSTO IIb,
desirudin was not associated with an improved long term clinical benefit at 30 days compared with
heparin. Similar results were seen in patients with
unstable angina/non-Q-wave MI enrolled in the GUSTO IIb trial. In addition,
desirudin and
heparin showed similar efficacy in preventing restenosis 30 weeks after coronary angioplasty for
unstable angina, despite
desirudin being associated with a significant reduction in the rate of
cardiac events within the first 96 hours.
Desirudin is as well tolerated as
heparin with a similar incidence of moderate and severe
bleeding, intracranial haemorrhage or
stroke reported when trialled in the prevention of DVT associated with hip replacement surgery or the treatment of
acute coronary syndromes. However, in the GUSTO IIb trial a significantly higher incidence of transfusions was observed in patients with
unstable angina/non-Q-wave MI.
CONCLUSIONS:
Desirudin is clearly more effective than
heparin in the prevention of DVT in patients undergoing elective hip replacement, although cost factors may influence its ultimate place in
therapy. In the treatment of
acute coronary syndromes the role of
desirudin is less certain; however, it may be useful for patients in whom
heparin therapy is not a viable option.