Desirudin: a review of its use in the management of thrombotic disorders.
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.
Matheson
A J
AJ
Adis International Limited, Mairangi Bay, Auckland, New Zealand. demail@adis.co.nz
Goa
K L
KL
D000787:Angina Pectoris / Q000150:complications; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D004334:Drug Administration Schedule; D006629:Hirudins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D009203:Myocardial Infarction / Q000150:complications; D011183:Postoperative Complications / Q000517:prevention & control; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control*
D000925:Anticoagulants; D006629:Hirudins; D011994:Recombinant Proteins; C060225:desirudin