Thrombin Generation in Patients with Acute Myocardial Infarction Treated with Front-Loaded rt-PA and Recombinant Hirudin (HBW 023).

Thrombin contributes to the pathogenesis of acute myocardial infarction and reocclusion after thrombolysis. Thrombolytic therapy is known to induce a paradoxic increase in thrombin generation. Specific thrombin inhibition enhances thrombolytic therapy in experimental models.

HBW 023 (recombinant hirudin) for the acceleration of thrombolysis and prevention of coronary reocclusion in acute myocardial infarction: results of a dose-finding study (HIT-II) by the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte.

Objective: To define an optimal dose of hirudin that would improve early coronary artery Thrombolysis in Myocardial Infarction grade 3 (TIMI 3) patency and prevent reocclusions in patients with acute myocardial infarction treated with front-loaded recombinant tissue-type plasminogen activator (rt-PA).

Methods: Recombinant hirudin (HBW 023) was tested in a sequential dose-escalating study as adjunct to front-loaded rt-PA in 143 patients with acute myocardial infarction. The sequential model was assigned two 'decision boundaries': it triggered an increase in dosage if the 60-min TIMI 3 flow rate in a dosage group was statistically not consistent with a target patency rate of 75%, or if the deterioration in coronary blood flow (of at least one TIMI grade, from TIMI 2 or 3, from one angiography to the next) exceeded 5%.

Recombinant hirudin (HBW 023) produces stable anticoagulation unaffected by circadian variation in patients with thrombolysis for acute myocardial infarction.

Background: Circadian variations have been described for a number of haemostatic and physiological factors, all of which might predispose towards clotting in the late morning. The anticoagulation effect of heparin has been shown to respond in a circadian manner, resulting in minimal prolongation of the activated partial thromboplastin time (aPTT) in the morning.

Methods: Recombinant hirudin (HBW 023) given as a bolus of 0.

Ulcer relapse rates following initial treatment with bismuth subnitrate as compared with cimetidine respectively.

As part of an open clinical trial, 18 out of 23 (78%) patients were treated with bismuth subnitrate (3 x 700 mg/d) and 15 out of 25 (60%) patients were treated with cimetidine (1 x 800 mg/d) to cure peptic ulcers linked with H. pylori, as ascertained following an endoscopic examination. All patients underwent continued observation after complete healing on completion of four weeks of acute treatment.