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: Z G Turi, S Goldberg, J K LittleJohn, C Vander Ark, N Shadoff, R Karlsberg, J Williams, S Butman, M L Stadius, K Wise
• Journal: The American journal of cardiology (Am J Cardiol) Vol. 71 Issue 12 Pg. 1009-14 (May 01 1993) ISSN: 0002-9149 [Print] United States
• PMID: 8475860 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Proteins
• Tissue Plasminogen Activator
• duteplase

Topics

• Adult
• Aged
• Dose-Response Relationship, Drug
• Female
• Hemorrhage (chemically induced)
• Humans
• Male
• Middle Aged
• Myocardial Infarction (drug therapy)
• Prospective Studies
• Recombinant Proteins (administration & dosage, adverse effects)
• Thrombolytic Therapy
• Tissue Plasminogen Activator (administration & dosage, adverse effects)
• Vascular Patency