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 adjun ctive therapy to thrombolysis with front-loaded tissue plasminogen act ivator (t-PA) (100 mg. 90 min(-1)) in 40 patients with acute myocardia l infarction whose duration of symptoms Was less than 6h. Patients rec eived a bolus of r-hirudin Of 0-07 mg.g. kg(-1) b.w. followed by an in fusion of 0.05 mg. kg(-1).h (-1) over 48 h. Complete patency (TTMI gra de 3) of the infarct-related artery at 30, 60 and 90 milt after the st art of thrombolytic therapy was seen in 38.5%, 64.1% and 71.0% of pati ents, respectively After 24-48 h, 80% of patients had a complete paten t infarct vessel. A very early, complete and sustained patency (TIMI g rade 3 at 60 and 90 min and at 24-48 h) was observed in 55% of patient s. Reocclusions during the hirudin therapy appeased in sh (16.1%) pati ents, 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 obser ved in three patients. Spontaneous organ bleedings and intracerebral h aemorrhages did not occur. There was one in-hospital death due to a la te retroperitoneal bleeding. In was concluded that, with regard to saf ety and efficacy, the general feasibility of r-hirudin as adjunctive t herapy to thrombolysis with front-loaded t-PA, has been demonstrated S ubsequently, a nose escalation study (HIT-II) with a sequential design has been started; three doses of r-hirudin, increasing in strength, a ve being investigated with regard to efficacy and safety.