Copyright © 2001 by the European Society of Cardiology.
Incidence and predictors of bleeding events after fibrinolytic therapy with fibrin-specific agents. A comparison of TNK-tPA and rt-PA
a Department of Cardiology, University of Leuven, Leuven, Belgium
b University of California San Francisco, San Francisco, U.S.A.
d Alberta University, Edmonton, Canada
e Duke Clinical Research Institute, Durham, U.S.A.
f Boehringer Ingelheim, Ingelheim, Germany
c Genentech, Inc. South San Francisco, U.S.A.
g Sourasky Medical Center, Tel Aviv, Israel
h Karolinska Institute, Stockholm, Sweden
i St. Radboudziekenhuis, Nijmegen, The Netherlands
j Johannes Gutenberg University, Mainz, Germany
k Hospital Clinic i Provincial de Barcelona, Barcelona, Spain
revised February 23, 2001; accepted February 28, 2001
Abstract
Background Fibrinolytic therapy increases the risk of bleeding events. TNK-tPA (tenecteplase) is a variant of rt-PA with greater fibrin specificity and reduced plasma clearance that can be given as a single bolus. We compared the incidence and predictors of bleeding events after treatment with TNK-tPA and rt-PA.
Methods and Results In the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-2 trial, 16949 patients with acute myocardial infarction were randomly assigned a single weight-adjusted bolus of TNK-tPA or a 90-min infusion of rt-PA. A total of 4·66% of patients in the TNK-tPA group experienced major non-cerebral bleeding, in comparison with 5·94% in the rt-PA group (P=0·0002). This lower rate was associated with a significant reduction in the need for blood transfusion (4·25% vs 5·49%,P =0·0003) and was consistent across subgroups. Independent risk factors for major bleeding were older age, female gender, lower body weight, enrolment in the U.S.A. and a diastolic blood pressure <70mmHg. Females at high risk (age >75 years and body weight <67kg) were less likely to have major bleeding when treated with TNK-tPA even after other risk factors were taken into account. A total of 0·93% of patients in the TNK-tPA and 0·94% of patients in the rt-PA group experienced an intracranial haemorrhage. Female patients >75 years of age who weighed <67kg tended to have lower rates of intracranial haemorrhage when treated with TNK-tPA (3/264, 1·14% vs 8/265, 3·02%).
Conclusions The increased fibrin specificity and single bolus administration of TNK-tPA do not increase the risk of intracranial haemorrhage but are associated with less non-cerebral bleeding, especially amongst high-risk patients.
Key Words: Fibrinolysis, haemorrhage, myocardial infarction, thrombolysis
f1 Correspondence: Frans Van de Werf, MD, PhD, Department of Cardiology, Gasthuisberg University Hospital, Herestraat 49, B-3000 Leuven, Belgium.
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