FREQUENCY OF OPTIMAL ANTICOAGULATION FOR ACUTE MYOCARDIAL-INFARCTION AFTER THROMBOLYSIS WITH FRONT-LOADED RECOMBINANT TISSUE-TYPE PLASMINOGEN-ACTIVATOR AND CONJUNCTIVE THERAPY WITH RECOMBINANT HIRUDIN (HBW-023)

This retrospective analysis reviewed 183 patients with acute myocardia l infarction who were given front-loaded recombinant tissue-type plasm inogen activator (rt-PA) and r-hirudin (HBW 023) in 1 of 4 dose groups (bolus dose of 0.07, 0.1, 0.2, or 0.4 mg/kg, followed by an infusion of 0.05, 0.06, 0.1, or 0.15 mg/kg/hour over 48 hours). Activated parti al thromboplastin time (aPTT) levels were determined at baseline and a t 4, 8, 12, 16, 20, 24, 32, 40, and 48 hours. Of the 178 patients with r-hirudin treatment for greater than or equal to 12 hours, anticoagul ation was optimal in 55.1% (all aPTTs > 2 X baseline), suboptimal in 3 3.7% (lowest aPTT > 1.5 but < 2 X baseline), and inadequate in 11.2% ( greater than or equal to 1 aPTT but < 1.5 X baseline). Optimal anticoa gulation was observed more frequently in the higher dose groups (dose 1, 15%; dose 2, 44.4%; dose 3, 63.4%; dose 4, 73.4%; p for trend < 0.0 001). Patency (according to Thrombolysis in Myocardial Infarction tria l grade 2 or 3) of the infarct artery after 36 to 48 hours was higher in the group with optimal anticoagulation compared with chose with sub optimal or inadequate anticoagulation: 97.9%, 88.4%, and 85%, respecti vely (p = 0.03 optimal vs suboptimal or inadequate anticoagulation). I n conclusion, r-hirudin in a dose of 0.1 or 0.15 mg/kg/hour achieves a n optimal anticoagulation in about 63% or 74% of patients, which is as sociated with an enhanced potency 24 to 48 hours after rt-PA. A subseq uent study revealed that this effective anticoagulation may be accompa nied by an increased risk of severe bleeding complications after throm bolysis.