JACC Vol. 19, No . 2 February 1992:295- 6
295
Editorial Comment As in all such studies, a numberof questions can be raised concerning the study of De Jaegere et al . (6). What clinical
Intracranial Hemorrhage After Thrombolytic Therapy : A Therapeutic Conflict*
criteria were, used to make the diagnosis of intracranial hemorrhage? Most but not all patients with this diagnosis had a computed tomographic (CT) scan of the brain . How was the presence of intracranial hemorrhage determined in patients who did not undergo CT scanning? How were registry data validated and standardized among the 61 insti-
JOSEPH S. ALPERT, MD, FACC tutions? What were the dose and route of administration Worcester, Massachusetts
when heparin was given? These and many other questions will need to be answered infuture conmsunicationsfrom this registry and others monitoring thrombolytic therapy . Even-
For extreme illnesses, extreme treatments are most fitting . tually, some of these issues will need to be addressed in Hippocrales, Aphorisms . 1 .6
more formal clinical trials . The importance of these ques-
As to diseases, make a habit of two things-to help, or at
tions is clear, because higher rates of intracranial hemor-
least do no harm .
rhage with attendant increased mortality may alter assessHippocrates, Epidemics . Bk . I . Sect . XI
ments of risk/benefit ratio in managing patients with acute myocardial infarction .
These two Hippocratic statements are well known to most
Predicting increased risk of intracranial hemorrhage .
physicians . The first is often cited when the physician
Given the very high mortality rate associated with intracra-
prepares for an aggressive intervention against a lethal
nial hemorrhage, cardiologists are anxiously seeking strate-
disease and the second when drugs or procedures are
gies to prevent or at least decrease the risk of its occurrence.
associated with iatrogenic complications . These two pieces
Several clinical factors have been associated with intracra-
of Hippocratic advice conflict when discussing thrombolytic
nial hemorrhage (Table 1) (5-7) . This does not mean that
therapy for acute myocardial infarction . On the one hand,
these factors necessarily cause intracranial hemorrhage ;
aggressive interventional therapy, including intravenous
they are merely associated with an increased risk of its
thrombolytic agents, has been repeatedly associated with
occurrence.
decreased in-hospital and long-term mortality after acute
Many clia ;cians avoid using thrombolytic agents in the
infarction . On the other hand, controlled trials and clinical
presence of these risk factors. In so doing, they may be
experience have clearly documented hemorrhagic deaths
rendering a disservice to their patients because the increased
secondary to thrombolytic therapy itself . Many of these
risk of dying from acute myocardial infarction treated con-
iatrogenic deaths are the result of intracranial hemorrhage .
ventionally may far outweigh the risk of intracranial hemor-
The present study. In most of the carefully controlled,
rhage . Clearly, more data from registries and controlled
randomized trials of thrombolytic therapy, the incidence of
trials are required to construct a complete picture of throm-
intracranial hemorrhage has been low (0.5% to 0 .6%), al-
bolytic therapy risk/benefit ratio in the presence of risk
though a frequency of up to 1 .6% has been reported (l-5). In
factors for intracranial hemorrhage.
this issue of the Journal, be Jaegere and coworkers (6)
An American patient with an acute myocardial infarction
report a high rate of intra .ranial hemorrhage (1%) in a
is approximately one-third to one-half as likely as his or her
registry of 2,469 patients with acute myocardial infarction admitted to 61 hospitals in the Netherlands . The clear implication of this study is tha+ registry patients are at higher Table 1. Factors Associated With Increased Risk of risk for intracranial hemorrhage compared with the highly tntracranial Hemorrhage selected population of the randomized controlled trials . Since the Dutch registry patients probably resemble nonstudy patients in the baited States, one anticipates that rates
Factors associated with increased risk in one study Use of anticoagulant drugs on admission'
of intracranial hemorrhage will also be higher in patients
Diabetes mellitus
with "routine" infarction treated with thrombolytic agents
Female gender' rt-PA dose 150 no as . 100 mg' Calcium channel blacker therapy on admission
in the United States .
Factors associated with increased risk in mine than nun study 'Editorials published in Joaerat of the American College of Cardiology reaecI the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology . From the Division ofCardiovascular Medicine, University of Massachusetts Medical Center, Worcester, Massachusetts. 9ddress fm reeriag: Joseph 0. Alpert, MD, Division of Cardiovascular Medicine, Ueivemily of Mausachuselts Medical Center, 55 take Avmae North, Worcester, Mamachusens 01655 .
®1592 by the American College of Cardiology
Older age (>(5 years)' Low body weight (
295
Editorial Comment As in all such studies, a numberof questions can be raised concerning the study of De Jaegere et al . (6). What clinical
Intracranial Hemorrhage After Thrombolytic Therapy : A Therapeutic Conflict*
criteria were, used to make the diagnosis of intracranial hemorrhage? Most but not all patients with this diagnosis had a computed tomographic (CT) scan of the brain . How was the presence of intracranial hemorrhage determined in patients who did not undergo CT scanning? How were registry data validated and standardized among the 61 insti-
JOSEPH S. ALPERT, MD, FACC tutions? What were the dose and route of administration Worcester, Massachusetts
when heparin was given? These and many other questions will need to be answered infuture conmsunicationsfrom this registry and others monitoring thrombolytic therapy . Even-
For extreme illnesses, extreme treatments are most fitting . tually, some of these issues will need to be addressed in Hippocrales, Aphorisms . 1 .6
more formal clinical trials . The importance of these ques-
As to diseases, make a habit of two things-to help, or at
tions is clear, because higher rates of intracranial hemor-
least do no harm .
rhage with attendant increased mortality may alter assessHippocrates, Epidemics . Bk . I . Sect . XI
ments of risk/benefit ratio in managing patients with acute myocardial infarction .
These two Hippocratic statements are well known to most
Predicting increased risk of intracranial hemorrhage .
physicians . The first is often cited when the physician
Given the very high mortality rate associated with intracra-
prepares for an aggressive intervention against a lethal
nial hemorrhage, cardiologists are anxiously seeking strate-
disease and the second when drugs or procedures are
gies to prevent or at least decrease the risk of its occurrence.
associated with iatrogenic complications . These two pieces
Several clinical factors have been associated with intracra-
of Hippocratic advice conflict when discussing thrombolytic
nial hemorrhage (Table 1) (5-7) . This does not mean that
therapy for acute myocardial infarction . On the one hand,
these factors necessarily cause intracranial hemorrhage ;
aggressive interventional therapy, including intravenous
they are merely associated with an increased risk of its
thrombolytic agents, has been repeatedly associated with
occurrence.
decreased in-hospital and long-term mortality after acute
Many clia ;cians avoid using thrombolytic agents in the
infarction . On the other hand, controlled trials and clinical
presence of these risk factors. In so doing, they may be
experience have clearly documented hemorrhagic deaths
rendering a disservice to their patients because the increased
secondary to thrombolytic therapy itself . Many of these
risk of dying from acute myocardial infarction treated con-
iatrogenic deaths are the result of intracranial hemorrhage .
ventionally may far outweigh the risk of intracranial hemor-
The present study. In most of the carefully controlled,
rhage . Clearly, more data from registries and controlled
randomized trials of thrombolytic therapy, the incidence of
trials are required to construct a complete picture of throm-
intracranial hemorrhage has been low (0.5% to 0 .6%), al-
bolytic therapy risk/benefit ratio in the presence of risk
though a frequency of up to 1 .6% has been reported (l-5). In
factors for intracranial hemorrhage.
this issue of the Journal, be Jaegere and coworkers (6)
An American patient with an acute myocardial infarction
report a high rate of intra .ranial hemorrhage (1%) in a
is approximately one-third to one-half as likely as his or her
registry of 2,469 patients with acute myocardial infarction admitted to 61 hospitals in the Netherlands . The clear implication of this study is tha+ registry patients are at higher Table 1. Factors Associated With Increased Risk of risk for intracranial hemorrhage compared with the highly tntracranial Hemorrhage selected population of the randomized controlled trials . Since the Dutch registry patients probably resemble nonstudy patients in the baited States, one anticipates that rates
Factors associated with increased risk in one study Use of anticoagulant drugs on admission'
of intracranial hemorrhage will also be higher in patients
Diabetes mellitus
with "routine" infarction treated with thrombolytic agents
Female gender' rt-PA dose 150 no as . 100 mg' Calcium channel blacker therapy on admission
in the United States .
Factors associated with increased risk in mine than nun study 'Editorials published in Joaerat of the American College of Cardiology reaecI the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology . From the Division ofCardiovascular Medicine, University of Massachusetts Medical Center, Worcester, Massachusetts. 9ddress fm reeriag: Joseph 0. Alpert, MD, Division of Cardiovascular Medicine, Ueivemily of Mausachuselts Medical Center, 55 take Avmae North, Worcester, Mamachusens 01655 .
®1592 by the American College of Cardiology
Older age (>(5 years)' Low body weight (
