(Stroke. 2000;31:1802.)
© 2000 American Heart Association, Inc.
Original Contributions |
Intracranial Hemorrhage Associated With Thrombolytic Therapy for Elderly Patients With Acute Myocardial Infarction
Results From the Cooperative Cardiovascular Project
From the Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, Conn (L.M.B., J.H.L., M.J.R., H.M.K.); Neurology Service, VA Connecticut Healthcare System, West Haven, Conn (L.M.B.); Yale Stroke Program, Department of Neurology (L.M.B., J.H.L.); Section of Chronic Disease Epidemiology, School of Epidemiology and Public Health (L.M.B., H.M.K.), and Department of Cardiology (H.M.K.), Yale University School of Medicine, New Haven, Conn; Qualidigm (L.M.B., Y.W., M.J.R., H.M.K.), Middletown, Conn; and Meyers Primary Care Institute, Fallon Healthcare System and University of Massachusetts Medical School, Worcester (J.H.G.).
Correspondence to Lawrence M. Brass, MD, Yale Stroke Program, Department of Neurology, LCI-700, Yale University School of Medicine, 15 York St, PO Box 208018, New Haven, CT 06520-8018. E-mail Lawrence.Brass{at}yale.edu
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Abstract |
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Background and Purpose—Intracranial hemorrhage is a serious complication of thrombolytic therapy for acute myocardial infarction, especially among the elderly, but little information exists on estimating risk. Better estimation of risk in individual patients may allow for withholding or using alternate therapies among those at highest risk.
Methods—To quantify the risk and identify predictors of intracranial hemorrhage associated with thrombolytic therapy, we performed a retrospective cohort study using data from medical charts. The study involved nearly all acute-care hospitals in the United States. All Medicare patients discharged with a principal diagnosis of acute myocardial infarction during a 9-month period in 1994 to 1995 were included. The main outcome measure was intracranial hemorrhage among those treated with thrombolytic therapy.
Results—The rate of intracranial hemorrhage was 1.43%
(455 of 31 732). In a logistic model, age 
75 years, female, black
race, prior stroke, blood pressure 160 mm Hg, tissue
plasminogen activator (versus other
thrombolytic agent), excessive anticoagulation
(international normalized ratio 4 or prothrombin time 24), and
below median weight (
65 kg for women; 80 kg for men) were
independent predictors. A risk stratification scale was developed on
the basis of these factors: with none or 1 of the factors (n=6651), the
rate of intracranial hemorrhage was 0.69%; with 2 factors
(n=10 509), 1.02%; with 3 factors (n=9074), 1.63%; with 4 factors
(n=4298), 2.49%; and with 5 factors (n=1071), 4.11%
(Mantel-Haenszel; P<0.001).
Conclusions—The rate of intracranial hemorrhage in older patients after treatment with thrombolytic therapy exceeds 1%. Readily available factors can identify elderly patients with acute myocardial infarction at high and low risk for intracranial hemorrhage associated with thrombolytic therapy.
Key Words: intracranial hemorrhage • myocardial infarction • risk factors • thrombolytic therapy
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Introduction |
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Thrombolytic therapy lowers the mortality rates for patients with suspected acute myocardial infarction (AMI) and ST-segment elevation or left bundle-branch block. It is the most widely used form of reperfusion therapy in the setting of an AMI and is part of standard emergency management.1 2 Many patients who are eligible for thrombolytic therapy may not be treated in part because of concern about specific patient characteristics associated with hemorrhagic complications, especially hemorrhagic stroke.3 4 5 6
Information about the risk of intracranial hemorrhage associated with thrombolytic therapy in clinical practice is limited, especially among the elderly,5 who are also at greater overall risk.7 Most of the information about the risk of hemorrhage comes from clinical trials or studies with small numbers of women and older patients; older patients in these trials tend to be highly selected. Given the poor prognosis for recovery, high mortality rate, and high health care costs associated with intracranial hemorrhage7 and the availability of alternate reperfusion strategies,8 identifying high-risk groups takes on special importance.
Our objectives were (1) to determine the rate of intracranial hemorrhage associated with thrombolytic therapy for elderly patients with AMI; (2) to identify independent predictive factors for intracranial hemorrhage; and (3) to develop an easily applied risk stratification scale for estimating the risk of intracranial hemorrhage among individual patients. To address these objectives, we analyzed data from >30 000 elderly patients treated with thrombolytic therapy included in the Cooperative Cardiovascular Project (CCP). The CCP is a geographically diverse, population-based cohort established as a collaborative project between the Health Care Financing Administration, healthcare professionals, and peer review organizations to examine patterns of care and stimulate improvements in the care and outcomes of Medicare beneficiaries with AMI.3 9 10 11
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Subjects and Methods |
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The CCP is a Health Care Financing Administration quality-improvement initiative focusing on the treatment of AMI.3 9 The study sample includes Medicare patients
65
years of age from nongovernmental acute-care hospitals with a principal
discharge diagnosis of AMI, International Classification of
Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code 410, with
those with a fifth digit of 2 (indicating subsequent episode of care)
excluded. Patients were identified during an 8-month period (varying in
each state) in 1994 and 1995 by means of hospital bills (UB-92 claims
data) in the Medicare National Claims History File.
Trained technicians abstracted predefined variables from copies of
the hospital record and entered them directly into a computer
database with use of interactive software. Data reliability was
monitored by random reabstractions, with overall variable agreement
averaging >90%. The agreement for whether patients had been treated
with thrombolytic therapy or not was 98.3%, and the
value was 0.93.12
The outcome variable for the study was the occurrence of intracranial hemorrhage during the hospitalization (ICD-9=430, 431, or 432). To assess the accuracy of our case ascertainment by using the discharge diagnoses, the outcome variable was compared with a separate variable abstracted from the medical record review that documented "any cerebrovascular accident" during the hospitalization (not specifically hemorrhagic). The agreement between the discharge diagnosis of a hemorrhagic stroke was >92%, indicating good accuracy for our method of case ascertainment.
Among those patients who received thrombolytic therapy,
we examined bivariate associations between candidate clinical
variables, selected on the basis of clinical judgment and prior
reports, and intracranial hemorrhage. By using independent
predictors from the bivariate analyses present in 5% of
the cohort, we developed a multivariable logistic regression model
by backward stepwise selection, with intracranial hemorrhage as
the dependent variable. Because of its strong association with
intracranial hemorrhage, we did make an exception and included
excessive anticoagulation, which was present in <5% of the cohort
in the regression model. Variables were dropped at a significance
of P<0.05. The Hosmer and Lemeshow goodness-of-fit test was
used to test the fit of the models.13 A risk
stratification scale was developed on the basis of the variables in
the logistic model and weighted on the basis of the magnitude of
the effect. All calculations were performed with the software program
PC-SAS 6.12. (SAS Corp).
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Results |
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Of the 218 663 eligible patients, 14.5% (31 732 of 218 663) received thrombolytic therapy during their hospitalization. The mean age for the study sample was 73.4 years (median 73 years). The rate of intracranial hemorrhage was 1.43% (455 of 31 732) among the group receiving thrombolytic therapy as compared with 0.17% (318 of 186 931) for patients in the CCP cohort who did not receive thrombolytic therapy (P=0.001). The vast majority of cases, 80.4%, had intracerebral hemorrhage (ICD-9=431); 6.5% had subarachnoid hemorrhage (ICD-9 430), and the remaining 13.1% had other or unspecified intracranial hemorrhage (ICD-9=432). The overall mortality rate at 6 months for the entire patient population was 26.8% (58 565 of 218 663). It was 19.4% (6141 of 31 732) for those treated with thrombolytic therapy. Among those treated with thrombolytic therapy, the 6-month mortality rate was 72.5% (330 of 455) for those who had an intracranial hemorrhage compared with 18.6% (5811 of 31 277) for those who did not have an intracranial hemorrhage (P<0.001).
Clinical factors and therapies, along with their associated rates of
intracranial hemorrhage, are shown in Table 1
. We examined the risk of
hemorrhagic stroke associated with each 10–mm Hg increase in blood
pressure (BP). On the basis of the results shown in Figure 1, a cutoff of 160 mm Hg (
29%
of the sample) was used for subsequent analyses. The same
strategy was used to establish the cutoff for diastolic BP
100 mm Hg (16% of the sample).
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Data on an international normalized ratio (INR) or prothrombin time
(PT) measurement were missing on 3882 patients. Of these, 98% (3798 of
3882) were not receiving anticoagulant therapy at the time of
admission, so the comparison reported in Table 1
compares those
with an elevated INR or PT with all other patients (ie, in the models,
the variable was coded as either excessive anticoagulation being
reported or not). To test for the effect of the missing values, a dummy
variable for the missing values was included in the model. This
variable was not significant, indicating that there is no
association between the missing INR or PT values and the outcome of
intracranial hemorrhage. The goodness-of-fit test was not
significant (P=0.21), indicating a good fit for the model.
Only the highest levels of anticoagulation were associated with an
increased risk of intracranial hemorrhage. For those with an
INR <2 (or a PT <15) (n=25 528), the rate of hemorrhage was
1.45%; for an INR 2 and <3 (or PT 15 and <20, n=1686), the rate
of hemorrhage was 1.54%; for an INR 3 and <4 (or PT 20
and <24, n=320), the rate of hemorrhage was 1.25%; and for an
INR 4 (or PT 24, n=316), the rate of hemorrhage was
2.85.
There was an increased hemorrhage rate associated with lower
body weight (Figure 2). Given the
consistent trend, the median weight was used for further
analyses. The hemorrhage rate for weight below the
median value (sex-specific values 65 kg for women and 80 kg for
men) was 1.74% as compared with 1.08% for those above the median
weight value (P=0.001). Similarly, the rates were higher for
body mass index below the specified cutoff values (25 and 30) as
compared with rates for body mass index above the cutoff values
(P=0.001 for each).
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Clinically relevant factors and variables selected from bivariate
analyses were entered into a multiple logistic regression.
Other factors that achieved statistical significance in bivariate
analyses were not included because of low prevalence (eg, shock
on admission, hemorrhage within 48 hours of admission, and
dementia). We did make an exception and include excessive
anticoagulation (INR 4 or PT 24) in the regression model because of
the clear association of excessive anticoagulation with a greatly
increased risk of intracranial hemorrhage14 15 and
the specific inclusion of excessive anticoagulation in the American
College of Cardiology/American Heart Association
guidelines on the management of AMI with thrombolytic
therapy (Table 2).1
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From the multivariable logistic model (backward stepwise), the
following factors were independent predictors of hemorrhagic stroke in
this cohort: age 75 years age (OR=1.57 [95% CI 1.30 to 1.90]);
female sex (OR=1.39 [1.15 to 1.67]); black race compared with
nonblack races (OR=1.63 [1.13 to 2.37]); prior stroke (OR=1.48 [1.10
to 2.00]); systolic BP 160 mm Hg on admission (OR=1.82
[1.51 to 2.21]); tissue plasminogen activator
(TPA) (versus other thrombolytics) (OR=1.57 [1.23 to
2.01]); and below median weight (65 kg for women and 80 kg for
men, OR=1.47 [1.21 to 1.77]). The goodness-of-fit statistic for the
final model had a probability value of 0.27, indicating a good fit for
the model.
From the variables selected by the logistic model, we developed a
risk stratification scale to estimate the risk of intracranial
hemorrhage in an individual patient. Since the odds ratios for
the selected variables were similar in magnitude (range 1.4 to
1.8), each factor was given the same weight. Because of the small
number of patients with 0 factors (n=928) and the similar rate of
hemorrhage for 0 or 1 factors, we combined these into a single
group (n=6721) with a rate of intracranial hemorrhage of
0.71%. Similarly, we combined those with 5 factors into a single
group (n=1032) with a rate of intracranial hemorrhage of
4.07%. The trend in this model of increasing risk for intracranial
hemorrhage with increasing number of factors was statistically
significant (Mantel-Haenszel; P<0.001). The median score
for the cohort was 2 factors (mean of 2.4±1.1 factors), indicating
that more than half of all elderly patients have a low risk (1%) for
a hemorrhagic stroke.
Using patients with none or 1 factor as the referent group (21%), we
determined the increase in risk associated with the cumulative number
of the factors in the prediction scale (Table 3). Patients with 2 factors displayed
odds similar to patients in the referent category (OR 1.41 [95% CI
1.01 to 2.00]). Patients with 3 factors had double the odds (OR=2.28
[1.66 to 3.18]), patients with 4 factors had >3 times the odds of
having a hemorrhagic stroke (OR=3.51 [2.51 to 4.97]), and patients
with 5 factors had almost 9 times the odds as the referent group
(OR=5.89 [3.89 to 8.89]). The goodness-of-fit statistic was not
significant, which indicated a good fit of the model.
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Approximately 11% of all intracranial hemorrhages occurred in
the 21% of the sample with none or 1 factor, 23% of
hemorrhages occurred in the sample with 2 factors, and 66%
of hemorrhages occurred in the 45% of the cohort that had 3
risk factors. Among those 65 to 74 years of age, 74% (14 233 of
19 393) were at low risk with 2 risk factors for intracranial
hemorrhage. Even among those 75 years of age, 25% (3021 of
12 210) had 2 risk factors for hemorrhage, even including
age as 1 risk factor.
Comment
We found an overall rate of thrombolysis-related
intracranial hemorrhage in this elderly cohort 3 times higher
than usually cited in published clinical trials and treatment
guidelines.1 16 17 Furthermore, the rate of
hemorrhage is strongly associated with easily determined
clinical factors. Finally, these same factors can identify the majority
of elderly patients who are at very low risk for
thrombolysis-related intracranial hemorrhage
and a minority of patients who are at greatly increased risk for
intracranial hemorrhage.
Rate of Hemorrhage
The rate of intracranial hemorrhage associated with
thrombolytic therapy is generally considered to be
about half a percent.18 19 20 21 22 23 This low rate has been derived
largely from clinical trials. The generalizability of this low rate of
intracranial hemorrhage to a broader population is limited by
the highly selected nature of patients enrolled in clinical
trials.24 Trials enrolled healthier subjects compared with
the patients in the community25 ; older patients and women
are particularly underrepresented.26 Higher
rates of intracranial hemorrhage have been reported in
community-based studies; the Second National Registry of Myocardial
Infarction (NRMI-2) reported a rate of intracranial hemorrhage
of 0.95%.7
Risk Factors
This large, national, community-based sample of elderly patients
with AMI treated with thrombolytic therapy is well
suited to identify characteristics associated with hemorrhagic stroke.
The CCP database is rich in clinical information, and our cohort
contains the biggest group of patients 75 years of age reported to
date. Among the clinical trials, there were often exclusions for those
beyond age 7027 28 or 75 years.29 30 31 32 33
Blacks have higher rates of both ischemic and hemorrhagic stroke compared with whites.34 They are also at higher risk for intracranial hemorrhage after thrombolysis in our cohort and others.7 35 The reasons for this are unclear; however, race remained an independent predictor in our study. Factors not included in our analyses might account for at least part of this association. For example, blacks have higher rates of chronic hypertension and poorer rates of BP control.36 This may render the intracranial vessels more susceptible to most forms of stroke, including hemorrhage associated with thrombolytic therapy.
Many studies report a higher rate of hemorrhagic stroke associated with thrombolytic therapy among women35 37 38 39 ; however, this effect may not remain significant after adjusting for other factors. Women treated with thrombolytic therapy tend to be older, more often have a history of hypertension, smoking, and diabetes, and take longer to present for treatment.38 40 Our report suggests that women are at higher risk for intracranial hemorrhage even after correcting for other common risk factors.7 35 41
Similarly, prior stroke was often an exclusion criterion for trials of thrombolytic therapy, so information on the prevalence of prior stroke and the associated risk for hemorrhagic stroke is limited.42 Where data are available, prior cerebrovascular events were associated with an increased risk of thrombolysis-related intracranial hemorrhage7 18 21 38 43 44 45 ; however, the increased risk has also been attributed to the older age and less favorable risk profile among patients with prior cerebrovascular events.45 Our multivariate model confirms an earlier report by Gurwitz et al7 that prior stroke is an independent predictor of intracranial hemorrhage.
In our model, we used systolic BP. In other studies, diastolic BP appeared to be more significant.38 The Thrombolytic Predictive Instrument Project46 found that excessive pulse pressure predicted intracranial hemorrhage better than systolic, diastolic, or mean BP, although this was based on a small number of cases. We did not find an advantage of using the pulse pressure, nor did Gore and colleagues.38
Weight has been reported to have an inverse relation with the risk of intracranial hemorrhage with thrombolytic therapy.7 35 38 43 Recommendation for weight-based dosing became widespread several years before the start of this study, based on results such as the TIMI-II.29 A lower body weight may result in higher serum concentration of medication, resulting in a greater degree of fibrinolytic activity25 and an increased risk for hemorrhage. It has been suggested that this effect may be seen with TPA but not streptokinase.43 Our results corroborate those of Gurwitz and colleagues,7 who suggested an inverse relation between body weight and intracranial hemorrhage.
Our results suggest that a nonlinear, weight-based dosing schedule with a lower (mg/kg) dose for lighter patients may be appropriate. This effect could help explain differences among TPA trials for acute ischemic stroke and may provide valuable insight for planning future trials.47 48 49
Most patents were treated with TPA. Nearly all of the remainder was treated with streptokinase. TPA has been associated with a higher rate (3 per 1000 treated patients) of intracranial hemorrhage than streptokinase.19 20 43 The difference may be more prominent among the elderly.39 Other studies have demonstrated that higher doses of TPA appear to further increase the rate of intracranial hemorrhage, as does the accelerated TPA regiment with intravenous heparin or combination thrombolytic therapy.7 29 35 38 42 The use of TPA, higher doses, and accelerated administration of thrombolytic agents, however, may achieve greater efficacy.42 Future studies may be able to more safely explore the best use of these more aggressive regiments by selecting subjects to minimize risk factors for intracranial hemorrhage.
We did not find a clearly increased risk associated with the overall use of warfarin; however, those excessively anticoagulated did have a higher rate of intracranial hemorrhage. Excessive anticoagulation was included in our model despite its low frequency. Excessive anticoagulation in the setting of AMI has been associated with an increased risk for intracranial hemorrhage with agents such as heparin or hirudin.23 Because of the exclusion of patients with a prolonged PT or significantly elevated INR, little information on the risk of thrombolytic therapy and anticoagulation with warfarin is available from clinical trial data sets. Observational studies have not had sufficient power to achieve statistical significance despite at least 1 study with a suggestive trend.25 Because excessive anticoagulation with warfarin is strongly and consistently related to intracranial hemorrhage and because it is specifically mentioned as a relative contraindication in national guidelines, we believed that its inclusion in the scale was justified.
Other contraindications for thrombolytic therapy associated with hemorrhagic risk were not included in the stratification scale because of concern of significant ascertainment bias or a low reported frequency in the cohort. For example, we did find an association between the documentation of dementia in the medical record and the occurrence of hemorrhage but did not include this in the model because of the low frequency of documentation and the potential for reporting bias.50 It would be of great interest to include dementia or cognitive dysfunction in a prospective evaluation. Among the elderly, amyloid angiopathy is associated with both intracerebral hemorrhages and cognitive decline. It has been reported as a risk factor for thrombolysis-related intracranial hemorrhage and deserves further study.51
Risk Stratification
Our findings extend the results of others reporting risk
stratification scales or models for intracranial
hemorrhage7 28 52 by including more cases and a
geographically diverse, population-based cohort. Simoons and
colleagues43 used pooled data derived mostly from clinical
trials. There were 150 patients with intracranial hemorrhage
and 294 matched control subjects. The overall risk for intracranial
hemorrhage in their cohort was 0.75%. Four factors
independently contributed to the risk for hemorrhage: age >65
years, body weight <70 kg, hypertension on admission (systolic
BP 170 mm Hg, diastolic BP 95 mm Hg, or
both), and the use of TPA. The probability of hemorrhage ranged
from 0.26% to 2.17%. In older age groups, the range of
hemorrhage was shifted upward.
The rate of intracranial bleeding in our lowest-risk group (age 65 to 74 years with no other risk factors) is 0.66%, which is very close to that predicted by Simmons’s model for 1 risk factor (ie, age >65 years with no other risk factors): 0.64%. Because we were able to include additional risk factors (7 in total), our model has a wider range of values, being able to identify those at high risk. At these higher risks, the net benefit for thrombolytic therapy may be lost.53
Selker and colleagues52 derived a model for intracranial hemorrhage by using pooled data from clinical trials and registries. It was based on 2 factors: age and pulse pressure. The range among 4 strata was 0.0% to 4.4% (mean 0.6±0.8%). Their instrument also predicts major bleeding, cardiac arrest, and death. For intracranial hemorrhage, however, the instrument was based on only a few events (n=18). Only a very small portion of patients in their database was >75 years of age or had significantly elevated acute BPs (ie, systolic BP >190 mm Hg). This observation may account for the low overall rate of intracranial hemorrhage of 0.6%.
Their predictive instrument is complicated, and it is not intended for a clinician to calculate a specific risk. The instrument was intended to be computed by a software program integrated into an ECG machine used in the emergency medical setting. The system also does not take into account other factors that have been shown in this and other studies to be predictive of hemorrhagic stroke.
Gurwitz and colleagues7 presented the relation between age and intracranial hemorrhage in men and women according to history of stroke. These results were adjusted for race, BP, and dose of TPA. They found an overall incidence of intracranial hemorrhage of 0.95%. Although this cohort included a broader range of patients than in most clinical trials and hence should be more reflective of the rate of intracranial hemorrhage in practice, the participating hospitals and the patients in this registry were selected, their study was restricted to TPA and included fewer elderly patients. Our risk stratification included all risk factors used in the previous instrument.
Low Risk
Concern for a possible stroke adversely influences both patient
and physician preferences for thrombolysis in the
setting of AMI.54 55 A disabling stroke is a feared
complication among patients, and it is often rated as the least
desirable outcome, even when death is included .56 57
Physicians appear to avoid the use of thrombolytic
therapy for patients with an increased risk of bleeding, especially
among the elderly.3
The availability of a widely applicable, simple system to stratify the
risk of hemorrhagic stroke may assist those devising
thrombolytic strategies by identifying patients at low
risk for hemorrhagic stroke. On the basis of our results, half of all
elderly patients are at low risk for intracranial hemorrhage.
The risk of patients with 2 risk factors is comparable to that seen
in the randomized controlled trials. This result points to a potent
opportunity to enhance the care of older patients with AMI by
increasing the appropriate use of thrombolytic therapy
among those at low risk for hemorrhage.
High Risk
Identifying those at high risk for intracranial hemorrhage
may assist in selecting those for alternate therapies for acute
reperfusion such as primary percutaneous transluminal
coronary angioplasty, which is associated with a lower rate of
intracranial hemorrhage.8
Our highest-risk group has a rate of intracranial hemorrhage exceeding 4%. A decision analysis has shown that thrombolytic therapy is favored for the treatment of suspected myocardial infarction in the elderly over a wide range of estimates; however, as the rate of a serious adverse event approaches 4%, the therapy has greater harm than benefit.58 Even if the therapy is beneficial on average, many patients and their physicians may not want to take a risk at a level as high as 2% of a catastrophic stroke. Others physicians, recognizing the high mortality rate of myocardial infarction in the elderly, may be willing to take a higher risk. Our study provides the best estimate of the risk of intracranial hemorrhage for older patients treated with thrombolytic therapy and should provide practical evidence for decisions made by patients and their physicians.
Our study does have several important limitations. Some relate to observation data59 60 and others are specific to this cohort.3 61 In observational studies there is the risk of a chance association (type I error). Although this is a possibility for some of the variables included in our scale, we limited our selection to variables that were clinically sensible to consider. In addition, each of the factors that remained in our multivariate model have been reported to be associated with intracranial hemorrhage in at least 1 previous report and were highly significant in the model.
Limitations of the CCP cohort have been reviewed in previous publications3 61 62 ; however, several items are worth reiterating for this report. The data were based on a retrospective chart review. Medical records are sometimes illegible or poorly organized. Although the reliability of abstracted data for this cohort has been reported to be high,61 patient characteristics may not have been documented in the medical record. This could limit our ability to identify important contraindications to therapy. Other potential risk factors, such as cholesterol, were not abstracted. We also did not have a record of the BP immediately before treatment; only the admission BP was recorded.
Age <65 years may be associated with a lower rate of
hemorrhage.43 Our cohort was limited to those 65
years of age.
The existence of intracranial hemorrhage was based on discharge diagnosis. Concern has been raised about the use of ICD-9-CM coding for ischemic stroke63 ; however, the diagnosis of hemorrhagic stroke has a greater specificity.34 64 Cases could have been missed if the clinical syndrome was not recognized. Most patients who have neurological signs or symptoms suggestive of a stroke do receive either a CT scan or MRI of the brain.7 We did not, however, have the specific results of brain imaging. We also did not have detailed information on the type of hemorrhage. Although most thrombolytic-associated hemorrhages are parenchymal and are readily identifiable on brain imaging, other types do occur.38 44
Finally, the risk stratification scale devised in the report remains to be externally validated and quantitatively compared with other risk stratification scales in an independent cohort.
Our study also has several strengths. Reports from clinical trials or voluntary registries may not reflect care provided across the United. States. Our results are based on a broad, population-based cohort that reflects actual practice patterns. It represents the most comprehensive evaluation of the risk of intracranial hemorrhage associated with thrombolytic therapy. In addition, the data were based on chart abstractions by trained professionals using standardized definitions with high reliability.
Conclusions
Our report extends previous reports on the rate and risk factors
for intracranial hemorrhage. Although we demonstrated that the
overall rate of intracranial hemorrhage is significantly higher
than usually quoted in trials and treatment guidelines, our risk
stratification scale can estimate the risk of hemorrhage in an
individual patient with the use of easily identifiable factors.
Withholding thrombolytic therapy or the selection of
alternate reperfusion strategies for the minority of elderly patients
at high risk may help avoid some cases of intracranial
hemorrhage.37 65 The use of our risk
stratification scale may help clinical decision-making and improve the
care of elderly by encouraging the appropriate use of
thrombolytic therapy.
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Acknowledgments |
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This study was supported in part by grant DF96-167 from the Patrick and Catherine Weldon Donaghue Medical Research Foundation, Hartford, Conn. Dr Krumholz is a Paul Beeson Faculty Scholar.
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Footnotes |
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The analyses on which this publication is based were performed under Contract Number 500-96-P549, entitled "Utilization and Quality Control Peer Review Organization for the State of Connecticut," sponsored by the Health Care Financing Administration, Department of Health and Human Services. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The author assumes full responsibility for the accuracy and completeness of the ideas presented. This article is a direct result of the Health Care Quality Improvement Program initiated by the Health Care Financing Administration, which has encouraged identification of quality improvement projects derived from analysis of patterns of care, and therefore required no special funding on the part of this contractor. Ideas and contributions to the author concerning experience in engaging with issues presented are welcomed.
Received March 1, 2000; revision received May 16, 2000; accepted May 16, 2000.
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