Recombinant hirudins: an overview of recent developments.
Hirudin is a specific thrombin inhibitor which acts independent of antithrombin III and is able to bind to fluid phase and clot bound thrombin. It has become available for clinical use by production with recombinant techniques just recently. Hirudin produces a relatively stable level of anticoagulation when compared with heparin. However, hirudin is not as effective as heparin in blocking thrombin generation, but is more effective than heparin in inhibiting thrombin activity. In patients with unstable angina, hirudin was more effective than heparin in preventing ischaemic events in the acute phase. This clinical benefit was no longer significant after 30 days in the Global Use of Strategies to open Occluded coronary arteries in acute coronary syndromes (GUSTO)-IIb study. Recombinant hirudins as adjunct to thrombolysis with alteplase do not significantly improve early patency, but decrease the rate of reocclusions. However, as an adjunct to streptokinase, hirudin improves the speed of reperfusion. The therapeutic range of hirudin in combination with thrombolysis is very narrow, as demonstrated by the increased rate of intracerebral bleedings in 3 clinical thrombolysis trials with higher doses of hirudin. Subsequent trials with markedly lower doses of hirudin did not show any increase in bleeding complications or any significant clinical benefit of hirudin compared to heparin as adjunct to thrombolysis. In a large trial comparing heparin and hirudin, patients with unstable angina scheduled for percutaneous transluminal coronary angioplasty (PTCA) had a similar event-free survival rate at 7 months, but hirudin reduced the incidence of early cardiac events. There is some evidence from large studies that hirudin is more effective than unfractionated and low molecular weight heparin in preventing deep vein thrombosis in patients who have had hip surgery. Furthermore, in a small trial in patients with established vein thrombosis, hirudin compared to heparin reduced the rate of new pulmonary embolism and the extension of venous thrombosis. Hirudin seems to be the treatment of choice for patients with heparin induced thrombocytopenia type II. It reduces the incidence of thromboembolic complications in this high risk patient group. To date, the considerably higher costs of recombinant hirudins compared to heparin does not justify their routine use, and it is appropriate to limit their use to individual cases where conventional thrombin inhibitors are contraindicated or much less effective.
Zeymer
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Städtische Kliniken Kassel, Medizinische Klinik II, Kassel, Germany.