Incidence and predictors of bleeding events after fibrinolytic therapy with fibrin-specific agents: a comparison of TNK-tPA and rt-PA.
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.


RESULTS
In the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-2 trial, 16 949 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 <70 mmHg. Females at high risk (age >75 years and body weight <67 kg) 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 <67 kg 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.
Van de Werf
F
F
Department of Cardiology, University of Leuven, Leuven, Belgium.
Barron
H V
HV
Armstrong
P W
PW
Granger
C B
CB
Berioli
S
S
Barbash
G
G
Pehrsson
K
K
Verheugt
F W
FW
Meyer
J
J
Betriu
A
A
Califf
R M
RM
Li
X
X
Fox
N L
NL
D000328:Adult; D000367:Age Factors; D000368:Aged; D000416:Alberta / Q000453:epidemiology; D001835:Body Weight; D002140:California / Q000453:epidemiology; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005060:Europe / Q000453:epidemiology; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000517:prevention & control*; D009657:North Carolina / Q000453:epidemiology; D010314:Partial Thromboplastin Time; D012307:Risk Factors; D012737:Sex Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects*
D005343:Fibrinolytic Agents; C104096:TNK-tissue plasminogen activator; D010959:Tissue Plasminogen Activator