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). ALKK Study Group.
This retrospective analysis reviewed 183 patients with acute myocardial infarction who were given front-loaded recombinant tissue-type plasminogen 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 partial thromboplastin time (aPTT) levels were determined at baseline and at 4, 8, 12, 16, 20, 24, 32, 40, and 48 hours. Of the 178 patients with r-hirudin treatment for > or = 12 hours, anticoagulation was optimal in 55.1% (all aPTTs > 2 x baseline), suboptimal in 33.7% (lowest aPTT > 1.5 but < 2 x baseline), and inadequate in 11.2% (> or = 1 aPTT but < 1.5 x baseline). Optimal anticoagulation 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 < 0.0001). Patency (according to Thrombolysis in Myocardial Infarction trial grade 2 or 3) of the infarct artery after 36 to 48 hours was higher in the group with optimal anticoagulation compared with those with suboptimal or inadequate anticoagulation: 97.9%, 88.4%, and 85%, respectively (p = 0.03 optimal vs suboptimal or inadequate anticoagulation). In conclusion, r-hirudin in a dose of 0.1 or 0.15 mg/kg/hour achieves an optimal anticoagulation in about 63% or 74% of patients, which is associated with an enhanced patency 24 to 48 hours after rt-PA. A subsequent study revealed that this effective anticoagulation may be accompanied by an increased risk of severe bleeding complications after thrombolysis.
D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects*; D016009:Chi-Square Distribution; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D024764:Hirudin Therapy; D006629:Hirudins / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D010314:Partial Thromboplastin Time; D010960:Plasminogen Activators / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012189:Retrospective Studies; D015912:Thrombolytic Therapy / Q000379:methods; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D006629:Hirudins; D011994:Recombinant Proteins; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator