Wb. Hillegass et al., INTRACRANIAL HEMORRHAGE RISK AND NEW THROMBOLYTIC THERAPIES IN ACUTE MYOCARDIAL-INFARCTION, The American journal of cardiology, 73(7), 1994, pp. 444-449
Thrombolytic therapy for acute myocardial infarction (AMI) has reduced
mortality at the expense of additional intracranial hemorrhages. To d
etermine whether this trade-off has been optimized, a decision analysi
s was performed using pooled data to determine the further reductions
in mortality required to justify increased intracranial hemorrhage rat
es from more potent thrombolytic and adjunctive antithrombotic regimen
s than intravenous streptokinase. Pooled data from large clinical tria
ls suggest that streptokinase has a 0.07% nonfatal intracranial hemorr
hage rate. Approximately 54% of these result in major/moderate disabil
ity and 46% in recovery or minor residual. The early mortality rate in
all AMI patients treated with thrombolytic therapy is 9.8%; it is 6.8
% in patients with inferior wall AMI and 17.9% in elderly patients. If
a new thrombolytic regimen provides a 1% absolute reduction in early
mortality compared with streptokinase therapy, approximately a greater
than or equal to 3.2% nonfatal intracranial hemorrhage rate is justif
ied to obtain this survival benefit. For a 10% relative reduction in m
ortality risk, the maximal acceptable nonfatal intracranial hemorrhage
rates are 2.2% for inferior wall AMI, 3.2% for all patients and 5.9%
for elderly patients. Whereas intracranial hemorrhage is a catastrophi
c complication of thrombolytic therapy in the treatment of patients wi
th AMI, thrombolytic regimens that result in significantly higher rate
s of intracranial hemorrhage than those observed with streptokinase ma
y be preferable at surprisingly smaller additional reductions in morta
lity. In addition to evaluating new thrombolytic and antithrombotic re
gimens, this analysis, in conjunction with models that predict patient
-specific intracranial hemorrhage risks and mortality benefits from th
rombolytic therapy, can Provide a framework for matching AMI patients
with optimal thrombolytic regimens.