RECOMBINANT HIRUDIN AND FRONT-LOADED ALTEPLASE IN ACUTE MYOCARDIAL-INFARCTION - FINAL RESULTS OF A PILOT-STUDY

Recombinant hirudin, a specific thrombin inhibitor, has been shown to accelerate thrombolysis and reduce reocclusions in experimental models. In a pilot trial recombinant hirudin (HBW 023) was used as apt adjunctive therapy to thrombolysis with front-loaded tissue plasminogen activator (t-PA) (100 mg. 90 min(-1)) in 40 patients with acute myocardial infarction whose duration of symptoms Was less than 6h. Patients received a bolus of r-hirudin Of 0-07 mg.g. kg(-1) b.w. followed by an infusion of 0.05 mg. kg(-1).h (-1) over 48 h. Complete patency (TTMI grade 3) of the infarct-related artery at 30, 60 and 90 milt after the start of thrombolytic therapy was seen in 38.5%, 64.1% and 71.0% of patients, respectively After 24-48 h, 80% of patients had a complete patent infarct vessel. A very early, complete and sustained patency (TIMI grade 3 at 60 and 90 min and at 24-48 h) was observed in 55% of patients. Reocclusions during the hirudin therapy appeased in sh (16.1%) patients, two of whom had a PTCA at 90 min. The only reinfarction was seen after 6h; this was successfully treated with additional thrombolysis. Major bIeedings, mostly related to the invasive procedure, were observed in three patients. Spontaneous organ bleedings and intracerebral haemorrhages did not occur. There was one in-hospital death due to a late retroperitoneal bleeding. In was concluded that, with regard to safety and efficacy, the general feasibility of r-hirudin as adjunctive therapy to thrombolysis with front-loaded t-PA, has been demonstrated Subsequently, a nose escalation study (HIT-II) with a sequential design has been started; three doses of r-hirudin, increasing in strength, ave being investigated with regard to efficacy and safety.