title: Dose-related efficacy and bleeding complications of double-chain tissue plasminogen activator in acute myocardial infarction. The Wellcome Tissue Plasminogen Activator Study Group.
abstract: Although the efficacy of recombinant tissue-type plasminogen activator (rt-PA) in acute myocardial infarction has been demonstrated, little formal dose-ranging information is available. This study examined the use of duteplase, the double-chain rt-PA subsequently used in the Third International Study of Infarct Survival, in a multicenter trial of 267 patients with evolving acute myocardial infarction assigned to receive 1 of 6 weight-adjusted doses. The primary end point was infarct vessel patency after 90 minutes of drug infusion. Patency was defined as Thrombolysis in Myocardial Infarction trial grade 2 or 3 perfusion, and was determined by an independent core laboratory masked to treatment assignment. Patency was present in 48% of patients receiving the lowest dose range and 78% of those receiving the highest, with an association between thrombolytic dose and patency (p = 0.009). The frequency of serious bleeding complications also correlated with the total dose of rt-PA infused (p = 0.003). Bleeding complications were primarily related to instrumentation; blood loss requiring transfusion or otherwise deemed clinically significant occurred in 12% of patients (central nervous system hemorrhage occurred in 1.1%). Thus, higher doses of rt-PA are associated both with increased efficacy and increased risk of serious bleeding complications. Weight-adjusted dosing may provide an optimal risk-benefit ratio for thrombolysis during acute myocardial infarction.
authors: Cardiac Catheterization Laboratory, Harper Hospital/Wayne State University School of Medicine, Detroit, Michigan 48201.
authors: Z G
authors: ZG
authors: Turi
authors: S
authors: S
authors: Goldberg
authors: J K
authors: JK
authors: LittleJohn
authors: C
authors: C
authors: Vander Ark
authors: N
authors: N
authors: Shadoff
authors: R
authors: R
authors: Karlsberg
authors: J
authors: J
authors: Williams
authors: S
authors: S
authors: Butman
authors: M L
authors: ML
authors: Stadius
authors: K
authors: K
authors: Wise
mesh_terms: D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects; D014654:Vascular Patency
chemical_list: D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; C068645:duteplase