Reactivation of coagulation after stopping infusions of recombinant hirudin and unfractionated heparin in unstable angina and myocardial infarction without ST elevation: results of a randomized trial

Aims To compare effects of heparin and hirudin on biochemical markers of co agulation. Methods and Results Patients (n=395) with unstable angina or myocardial inf arction without ST elevation were randomized to a 72-h infusion of one of t hree regimens: unfractionated heparin (bolus of 5000 IU followed by an infu sion of 1200 IU.h(-1)), low-dose hirudin (HBW 023; 0.2 mg. kg(-1) bolus fol lowed by 0.10 mg. kg(-1). h(-1)) or medium-dose hirudin (0.4 mg. kg(-1) bol us followed by 0.15 mg . kg(-1) . h(-1)). Infusions were adjusted to mainta in an activated partial thromboplastin time of between 60-100 s. Activated partial thromboplastin time, prothrombin fragment 1.2 (F1.2), thrombin anti thrombin III complex and D-dimer were measured before, during and after the infusion. Median activated partial thromboplastin time was similar in the two groups early on, but was significantly lower in the heparin group than in the combined hirudin group 48 h after starting the infusion (53 s and 75 s? respectively; P<0.001), and 6h after stopping (31 s and 46 s, respectiv ely; P<0.001). Median F1.2 levels were not significantly different between the groups during the infusion. Median thrombin antithrombin III levels in the heparin and hirudin groups were 2.8 mu g . l(-1) and 2.3 mu g. l(-1), r espectively, at 6 h (P<0.001), and 3.0 mu g . l(-1) and 23 mu g. l(-1), res pectively, at 48 h (P<0.001). Median D-dimer levels were 320 ng . ml(-1) an d 260 ng . ml(-1) 48 h after starting the infusion in the heparin and hirud in groups, respectively (P<0.001), and 415 ng . ml(-1) and 280 ng . ml(-1): respectively (P<0.001) 6h after stopping. D-dimer levels were significantl y elevated above baseline values in both groups 24-48 h after stopping the infusions. Conclusions The greater reduction of thrombin antithrombin III and D-dimer during the hirudin infusion supports the hypothesis that hirudin is a more potent antithrombin agent than heparin. Increased D-dimer levels after stop ping heparin or hirudin suggest that there is an ongoing pro-coagulant stat e. These results point to the greater efficacy of hirudin in preventing ear ly clinical events (death, myocardial infarction and refractory ischaemia) compared with heparin that have been observed in large randomized trials. P ersistent activation of coagulation after stopping infusions in our study s uggests that a longer course of antithrombotic treatment may be needed to p acify the thrombus. (C) 2000 The European Society of Cardiology.