RECOMBINANT HIRUDIN AS A PERIPROCEDURAL ANTITHROMBOTIC IN CORONARY ANGIOPLASTY FOR UNSTABLE ANGINA-PECTORIS

Percutaneous transluminal coronary angioplasty is often complicated by thrombotic abrupt vessel closure in patients with unstable angina pec toris. The present multicentre trial was performed to determine the fe asibility of two-dose regimens of recombinant hirudin (r-hirudin) comp ared to standard heparin in patients undergoing coronary angioplasty f or unstable angina, and to investigate the effects of the different tr eatment regimen on markers of coagulation activation. At five particip ating centres, 61 patients were randomly enrolled in one of two sequen tial groups of r-hirudin (group 1: 0.3 mg.kg(-1) i.v. bolus, 0.12 mg.k g(-1), h(-1) i.v. infusion; 21 patients; group 2: 0.5 mg. kg(-1) i.v. bolus, 0.24 mg.kg(-1).h (-1) i.v. infusion; 19 patients) or in a hepar in control group (150 IU.kg(-1) i.v. bolus, 20 IU.kg(-1).h(-1) i.v. in fusion; 21 patients). Antithrombotic therapy was started immediately b efore coronary angioplasty and continued for 24 h. This was followed b y a low-dose anticoagulant infusion for another 24 h (r-hirudin: 0.04 mg.kg(-1).h(-1); heparin: 7 IU.kg(-1).h(-1)). Activated partial thromb oplastin time, r-hirudin plasma concentrations by both immunological a nd functional assay, thrombin-hirudin complex, thrombin-antithrombin I II complex, soluble fibrin, and prothrombin fragment 1+2 were closely monitored. The median partial thromboplastin time prolongations at 24 h vs baseline were found to be 1.9-fold and 2.3-fold in r-hirudin grou p 1 and dose group 2, respectively, and 3.0-fold in the heparin group. There was a dose-dependent correlation between partial thromboplastin time and the r-hirudin plasma levels (r=0.61). In five of 21 patients of dose group 1, three of 19 patients of dose group 2. and 10/21 pati ents of the heparin group, partial thromboplastin time values exceedin g the predefined target range prompted an interruption of the infusion . One major bleeding complication occurred in dose group 2. The functi onal assay for the estimation of r-hirudin plasma concentrations showe d excellent correlations to the immunological technique (r=0.99). Diff erences between the thrombin-hirudin complex levels could not be obser ved. Increased concentrations of thrombin-antithrombin III complex, so luble fibrin, and prothrombin fragment 1+2 were seen 4-8 h after coron ary angioplasty and after reduction of the high-dose therapy in dose g roup 1 when compared with dose group 2 and the heparin group, respecti vely. Based on coagulation tests the present study showed the feasibil ity of a periprocedural antithrombotic regimen with r-hirudin for pati ents undergoing coronary angioplasty for unstable angina. In addition to the partial thromboplastin time the determination of r-hirudin plas ma levels by a chromogenic substrate assay considerably improves the m onitoring of therapy. The lower dose r-hirudin regimen seems to be sub optimal as periprocedural anticoagulation in coronary angioplasty pati ents as indicated by markers of thrombin generation and thrombin activ ity.