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Thrombolysis for Acute Stroke in Routine Clinical Practice
Dawn M. Bravata, MD;
Nancy Kim, MD;
John Concato, MD, MPH;
Harlan M. Krumholz, MD, MSc;
Lawrence M. Brass, MD
Arch Intern Med. 2002;162:1994-2001.
ABSTRACT
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Background Studies have demonstrated that thrombolytic therapy for acute stroke
can be given safely and effectively in study settings with experienced clinicians,
but the patient outcomes associated with thrombolytic therapy in routine clinical
practice require investigation.
Objectives To compare outcomes among patients given intravenous thrombolysis in
routine clinical practice with the results of the National Institute of Neurological
Disorders and Stroke rt-PA Study (NINDS cohort) and to examine whether protocol
deviations are associated with adverse events.
Methods Retrospective cohort of community-based patients given thrombolysis
for acute stroke from May 1, 1996, through December 31, 1998, in 16 Connecticut
hospitals (Connecticut cohort).
Results Forty-two (67%) of 63 patients in the Connecticut cohort had at least
1 major protocol deviation, and 61 (97%) had major or minor protocol deviations.
Overall, the in-hospital mortality was higher in the Connecticut cohort (16/63
[25%]) compared with the NINDS cohort (40/312 [13%]; P
= .01). The serious extracranial hemorrhage rate was also higher for the Connecticut
cohort (8/63 [13%] vs 5/312 [2%]; P = .001). Patients
in the Connecticut cohort without major protocol deviations had outcomes similar
to those in the NINDS cohort; however, patients in the Connecticut cohort
with major protocol deviations had higher rates of in-hospital mortality (13/42
[31%] vs 40/312 [13%]; P = .002) and serious extracranial
hemorrhage (7/42 [17%] vs 5/312 [2%]; P = .001).
Conclusions Protocol deviations occur commonly when thrombolytic therapy is given
to stroke patients in routine clinical practice. Patients who receive thrombolysis
with major protocol deviations have higher rates of in-hospital mortality
and serious extracranial hemorrhage than patients in the NINDS cohort.
INTRODUCTION
ACUTE ISCHEMIC STROKE is a major medical problem in the United States,
where approximately 600 000 new events occur each year. Although few
specific treatment options exist, thrombolytic therapy with tissue plasminogen
activator (tPA) improved neurological outcomes in a randomized controlled
trial.1-2 The beneficial effects
of tPA therapy appear to be long lasting2 and
cost-effective,3 and thrombolytic therapy is
now part of nearly every treatment guideline and consensus statement for acute
ischemic stroke.4 Despite these recommendations
regarding the use of thrombolytic therapy, only a minority of eligible patients
are treated with tPA,5-6 and national
efforts are under way to increase the use of tPA.
Although enthusiasm for tPA therapy in acute ischemic stroke is strong,
little information exists about whether the results of the clinical trials
can be replicated in clinical practice. Of the available studies, most have
reported favorable clinical outcomes and low rates of intracranial hemorrhage,
but these have been based on voluntary reporting7-9
or administrative data,10 have originated from
centers that participated in clinical trials of thrombolysis,8, 11
or have come from centers that had experience with protocols for acute stroke
care.5, 7, 12-13
Other data have suggested cause for concern. Results of a statewide,
mailed survey of neurologists and emergency medicine physicians documented
that, even among those who had prescribed tPA, knowledge of its contraindications
was poor.14-15 Overall, less than
20% of the respondents were able to identify cases with definite exclusion
criteria. A study of Indianapolis, Ind, hospitals suggested a rate of symptomatic
intracranial hemorrhage twice as high (12%) as that reported in the National
Institute of Neurological Disorders and Stroke rt-PA Study (NINDS) (6%).16 A report from hospitals in the Cleveland, Ohio, area
found a rate of symptomatic intracranial hemorrhage (16%) nearly 3 times higher
than that of the NINDS trial.17 The same report
found deviations from national treatment guidelines in half of the treated
patients.
The Cleveland report suggested that the community experience with tPA
for acute ischemic stroke may differ from that of the clinical trials, but
this study was limited to a single metropolitan area, nearly all cases had
the direct involvement of a neurologist, and the study did not include a comprehensive
review of medical records. Consequently, only a few potential protocol deviations
were assessed, and extracranial bleeding complications, commonly seen in thrombolytic
therapy for myocardial infarction, were not considered.
Therefore, to our knowledge, no study has comprehensively evaluated
whether tPA protocols are being adhered to in routine clinical practice, although
the importance of adhering to stroke tPA protocols has been established by
clinical trials.1, 18 It is therefore
essential to determine whether thrombolytic therapy is, or can be, used safely
in the community.
The objectives of the current study were to compare the outcomes of
patients given tPA in routine clinical practice with the results of the NINDS
trial, and to determine whether protocol deviations are associated with higher
rates of adverse events. We herein report the tPA experience in Connecticut
across a broad range of practice settings, using a detailed medical record
review that included a comprehensive assessment of possible protocol deviations
and clinical outcomes.
PATIENTS AND METHODS
DESIGN AND SETTING
We performed a comprehensive medical record review of patients given
tPA for a diagnosis of acute ischemic stroke at 16 acute care hospitals in
Connecticut from May 1, 1996, to December 31, 1998. Institutional review board
approval was obtained at all participating hospitals.
The goal of the sample selection was to include all patients in the
state of Connecticut who had received tPA for a diagnosis of stroke during
our study period. Therefore, we included all hospitals where the investigators
had personal knowledge that tPA had been given for stroke. For other acute
care hospitals in the state, we inquired of the chairpersons of the departments
of neurology and/or emergency medicine if they knew of any occasions when
tPA had been prescribed for stroke during the study period and included the
hospitals where the chairperson thought that tPA had been prescribed. Some
acute care hospitals in Connecticut had policies in place that stated that
they did not give tPA for stroke; we did not include these hospitals in our
study.
PATIENT IDENTIFICATION
We used several strategies to identify patients who received tPA for
acute stroke. The primary identification method consisted of using hospital
administrative data and looked at both an International
Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code for stroke or transient ischemic attack (430.0-438.9)
and a procedure code for intravenous thrombolysis or anticoagulation. We used
additional (secondary) approaches to avoid missing patients owing to variations
in coding practices: we searched hospital pharmacy databases, examined hospital
stroke team records, and surveyed emergency department physicians and chairpersons
of the neurology departments. Finally, to confirm these procedures, we examined
50% of the medical records of all patients discharged with a diagnosis of
stroke for 1 year at one of the participating hospitals. These 4 confirmatory
methods did not identify any additional patients receiving tPA beyond those
identified with the primary ascertainment scheme.
MEDICAL RECORD REVIEW
Two of us (D.M.B. and N.K.) abstracted the medical record data using
standard definitions and an extraction form developed for this study. These
authors were not involved in the clinical care of any of the patients included
in this study. Any coding uncertainties were documented, resolved by consensus
by 3 of us (D.M.B., N.K., and L.M.B.), and recorded in a coding dictionary.
Two of us (D.M.B. and N.K.) reviewed 10% of the medical records to assess
interrater reliability. A comparison of these charts demonstrated complete
coding agreement for all abstracted variables, confirmed that both authors
used the same methods for recording questions about the medical record data,
and established that both authors had documented the same information when
there was conflicting or uncertain data recorded in the medical record.
STROKE SEVERITY
The stroke severity for the patients in the NINDS trial was evaluated
using the National Institutes of Health Stroke Scale (NIHSS). To compare the
stroke severity of patients in the Connecticut cohort with that of the NINDS
cohort, we converted descriptions of admission stroke symptoms into an NIHSS
score using previously described techniques.19-20
We used 3 severity categories (0-10, 11-20, and >20) based on analyses from
the NINDS trial.21
OUTCOME MEASURES
Patient Outcomes
We examined in-hospital mortality, intracranial hemorrhage (symptomatic
and asymptomatic), and extracranial hemorrhage (serious and minor). In-hospital
mortality was defined as death owing to any cause at any time during the admission.
Intracranial hemorrhages were defined as hemorrhages that were reported on
any brain imaging study performed after admission. Symptomatic intracranial
hemorrhage was defined as an intracranial hemorrhage with the new onset of
an appropriate syndrome (eg, headache, change in mental status, or decreased
motor function). Serious extracranial hemorrhages were defined as symptomatic
extracranial bleeding, including lower extremity, genitourinary, gastrointestinal,
orbital, retroperitoneal, pulmonary, or intra-articular hemorrhage. Minor
extracranial hemorrhages were defined as asymptomatic bleeding, including
mucosal bleeding, purpura, petechiae, bruising, epistaxis, asymptomatic heme-positive
stool, asymptomatic vaginal bleeding, microscopic hematuria, central access
site bleeding, or asymptomatic intraparenchymal pulmonary hemorrhage (hemoptysis).
We also recorded the administration of blood transfusions and other therapies
for extracranial bleeding.
Protocol Deviations
A protocol deviation was defined as any deviation from the American
Heart Association (AHA) Guidelines for Thrombolytic Therapy for Acute Stroke.4 Major protocol deviations were defined as the presence
of any item classified as a contraindication on the tPA package insert, all
of which were included in the AHA guidelines. Minor protocol deviations were
defined as any item listed in the AHA guidelines that was not classified as
a major protocol deviation (eg, admission blood glucose level of <50 mg/dL
[<2.8 mmol/L] or >400 mg/dL [>22.2 mmol/L]). Other related factors were
also assessed, including process variables (eg, recording a patient's weight)
and contraindications to the use of thrombolytic therapy for myocardial infarction
(eg, motor vehicle collision within the previous 6 months). We also examined
the medical record for documentation of whether the clinicians were aware
of the presence of protocol deviations.
STATISTICAL ANALYSIS
The baseline characteristics and outcomes of the Connecticut and NINDS
cohorts were compared using t tests for dimensional
variables and Fisher exact and  2 tests for binary variables.
The Bonferroni method was used to adjust for multiple comparisons (for the
3 patient outcome measures); the null hypothesis for these comparisons was
rejected when the 2-sided P values were less than
.016.
RESULTS
Sixty-three patients were given tPA in 10 of the 16 hospitals surveyed.
These 10 hospitals were diverse in terms of size, location, academic affiliation,
and stroke services. Only 1 of the 10 hospitals had neurology and radiology
in-hospital services available 24 h/d. Nine hospitals had internal medicine
or family practice house staff, including 3 with neurology house staff. The
baseline characteristics of the patients in the Connecticut (n = 63) and the
NINDS (n = 312) cohorts who received tPA differed with respect to race, history
of prior stroke, and diastolic blood pressure, but we found no difference
in stroke severity as measured by the NIHSS except for the moderate severity
category (NIHSS, 11-20) (Table 1).
All 63 patients in the Connecticut cohort underwent non–contrast-enhanced
computed tomographic (CT) scanning of the head at admission, with results
as follows: normal in 12 (19%); old infarct in 18 (29%); acute infarct in
13 (21%); mass effect, edema, or sulcal effacement in 6 (10%); and new blood
in 1 (2%); hydrocephalus in 1 (2%); atrophy in 31 (49%); calcification in
6 (10%); white matter disease in 8 (13%); and plaque or atherosclerosis in
1 (2%).
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Table 1. Baseline Characteristics of Patients Receiving tPA in the
Connecticut and NINDS Cohorts*
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ADVERSE EVENTS
In-hospital mortality was substantially higher in the Connecticut cohort
(16/63 [25%]) compared with the NINDS cohort (40/312 [13%]; P = .01) (Table 2). The
NINDS reported data for 30-day mortality, whereas the Connecticut data refer
to in-hospital mortality (3 of the 16 deaths occurred within the first 24
hours after the administration of the tPA; 9, between the second and seventh
day; 3, during the second week; and the final death, on hospital day 36).
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Table 2. Total Adverse Events for Patients Receiving tPA in Connecticut
vs NINDS Cohorts*
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The rate of any intracranial hemorrhage in the Connecticut cohort was
11 (17%) of 63 compared with 34 (11%) of 312 in the NINDS cohort (P = .14) (Table 2). The
rates of symptomatic intracranial hemorrhages were similar in the Connecticut
(4/63 [6%]) and NINDS (20/312 [6%]) cohorts (P =
.99). The asymptomatic intracranial hemorrhage rates were higher in the Connecticut
(7/63 [11%]) than in the NINDS (14/312 [4%]) cohorts, but this difference
did not reach statistical significance (P = .04).
Given that the NINDS trial identified intracranial hemorrhages on the basis
of a CT scan at 24 hours, we examined the time from symptom onset to CT scan
in our cohort. Sixty-two of 63 patients received at least a second CT during
their admission (in addition to the admission CT scan on the day of symptom
onset), 57 within 24 hours of admission, and 5 within 48 hours of admission.
Of the 11 patients with any new intracranial hemorrhage, 10 had a second CT
scan within 24 hours. One patient had a second CT scan within 48 hours of
symptom onset, and his intracranial hemorrhage was asymptomatic.
The rate of serious extracranial hemorrhages was much higher in the
Connecticut cohort (8/63 [13%] vs 5/312 [2%]; P =
.001). Rates of minor extracranial hemorrhages were similar (Connecticut cohort,
17/63 [27%]; NINDS cohort, 72/312 [23%]; P = .51).
In the Connecticut cohort, 6 patients (10%) were given blood transfusions,
3 (5%) were given phytonadione (vitamin K), 3 (5%) were given fresh frozen
plasma, 2 (3%) were given cryoprecipitate, and 1 (2%) underwent surgery specifically
for extracranial bleeding.
PROTOCOL DEVIATIONS
Forty-two (67%) of the 63 patients treated with tPA in Connecticut had
at least 1 major protocol deviation, and 57 (90%) had at least 1 minor protocol
deviation. Overall, 61 (97%) had at least 1 protocol deviation (major or minor).
The 4 most common major protocol deviations were tPA dosing errors (ie,
dose >0.9 mg/kg; total dose >90 mg; or bolus >10% of total dose) in 22 (35%);
initiation of therapy more than 3 hours after symptom onset (including patients
with unknown symptom onset or awakening with symptoms) in 14 (22%); known
bleeding diathesis (ie, prothrombin time of >15 seconds, elevated activated
partial thromboplastin time, or platelet count of <100 x103/µL) in 6 (10%); and evidence of active internal bleeding in 5
(8%) (Table 3). These 4 protocol
deviations accounted for 47 (85%) of all 55 major deviations. The most common
minor protocol deviations included lack of blood pressure monitoring per AHA
recommendations (50/63 [79%]); lack of a stroke diagnosis made by a neurologist
or clinician using an NIHSS (13/63 [21%]); the presence of edema, shift, or
herniation on the admission CT image (6/63 [10%]); and the use of an antithrombotic,
anticoagulant, or antiplatelet medication within 24 hours after tPA therapy
(6/63 [10%]) (Table 4). Together,
these 4 protocol deviations accounted for 75 (89%) of all 84 minor protocol
deviations.
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Table 3. Major Protocol Deviation Frequency and Adverse Event Rates
in the Connecticut Cohort*
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Table 4. Minor Protocol Deviation Frequency and Adverse Event Rates
in the Connecticut Cohort*
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In-hospital mortality increased as the number of major protocol deviations
increased. The in-hospital mortality rate was 3 (14%) of the 21 patients with
no major protocol deviations, 9 (29%) of the 31 patients with 1 major protocol
deviation, and 4 (36%) of the 11 with 2 or more major protocol deviations.
A similar relationship was found for the number of minor protocol deviations
and in-hospital mortality (no deviations, 1/6 [17%]; 1, 8/35 [23%];  2,
7/22 [32%]).
When we compared the results of the Connecticut and NINDS cohorts, we
found that the mortality rates were similar for the patients in the Connecticut
cohort without major protocol deviations and the NINDS cohort (Connecticut,
3/21 [14%]; NINDS, 40/312 [13%]; P = .85), and rates
of serious extracranial hemorrhage were also similar (Connecticut, 1/21 [5%];
NINDS, 5/312 [2%]; P = .29). The mortality for patients
in the Connecticut cohort with at least 1 major protocol deviation was much
higher than the mortality of the NINDS patients (Connecticut, 13/42 [31%];
NINDS, 40/312 [13%]; P = .002) (Table 5). Similarly, serious extracranial hemorrhage was more common
among patients in the Connecticut cohort with at least 1 major protocol deviation
(Connecticut, 7/42 [17%]; NINDS, 5/312 [2%]; P =
.001).
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Table 5. Comparison of Adverse Outcomes Between the NINDS and Connecticut
Cohorts With or Without Major Protocol Deviations*
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When comparing patients treated despite major protocol deviations with
the patients without major protocol deviations, no statistical differences
were found with respect to age, sex, ethnicity, and stroke severity (Table 6). However, the mean age for patients
with protocol deviations was higher, and a greater proportion of patients
with protocol deviations were in the most severe stroke category. To determine
whether the excess mortality seen in patients with major protocol deviations
was due to differences in stroke severity, we examined the in-hospital mortality
within stroke severity stratum. The in-hospital mortality was the same or
worse among patients with major protocol deviations compared with those without
major protocol deviations in each of the stroke severity categories (Table 7).
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Table 6. Patient Characteristics of the Connecticut Cohort by Major
Protocol Deviation Status*
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Table 7. In-Hospital Mortality by Major Protocol Deviations and Stroke
Severity in the Connecticut Cohort*
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Several processes of care were not categorized as protocol deviations
because they are not included in the AHA guidelines; however, they are clinically
relevant. For example, although tPA dosing is weight based, in 22 (35%) of
the 63 patients in the Connecticut cohort, no actual or estimated weight was
recorded before the tPA was administered. Furthermore, results of a rectal
examination were not documented in 18 (29%) of 63 patients. Three patients
had a history of recent trauma or motor vehicle collision, and all of these
patients had an adverse event. For 2 patients the trauma or motor vehicle
collision occurred on the day of stroke symptom onset (one patient died; the
other had an intracranial hemorrhage and was transferred to a facility with
neurosurgical expertise); for 1 patient the trauma or collision occurred 2
months before the stroke onset (this patient had a major extracranial hemorrhage).
We also evaluated the relationship between a particular hospital's experience
(ie, the total number of patients receiving tPA for stroke during the study
period) and the number of major or minor protocol deviations. The number of
patients treated at any single hospital ranged from 1 to 16; patient volume
was not related to the type or size of the hospital. In addition, no relationship
appeared to exist between patient volume and the number of major or minor
protocol deviations (data not shown).
We examined the relationship between patient outcomes and the clinicians'
knowledge about the existence of protocol deviations before ordering the tPA.
For 19 (30%) of the 63 patients, the clinicians documented that they were
aware of the protocol deviation. The in-hospital mortality, however, was not
related to whether the clinicians had documented that they were aware of the
protocol deviation (aware, 6/19 [32%]; unaware, 10/44 [23%]; P = .46).
Patients without major protocol deviations had better discharge dispositions,
including mortality, than patients with major protocol deviations. For example,
1 (2%) of the 42 patients with a major protocol deviation was discharged home
independently (ie, without visiting nurse assistance), compared with 5 (24%)
of the 21 patients without a major protocol deviation. Viewed from another
perspective, among the 6 patients who were discharged to home without visiting
nurse assistance, 5 (83%) had been treated without major protocol deviations,
whereas 1 (17%) had been treated with a major protocol deviation (P = .025).
COMMENT
We found higher overall rates of hemorrhage (serious intracranial and
extracranial bleeding, 19%; total extracranial bleeding, 37%; and total intracranial
bleeding, 17%) and mortality (25%) associated with tPA use than previously
reported in the published literature. These findings suggest that the clinical
application of thrombolytic therapy has not replicated the results of the
clinical trials. Serious protocol deviations occur in two thirds of all cases,
and hemorrhagic complications and mortality rates are significantly higher
than those seen in clinical trials. These adverse outcomes occur more frequently
in patients who were treated despite deviations from treatment guidelines.
Two findings lend strength to the conclusion that major protocol deviations
were associated with adverse outcomes within the Connecticut cohort and were
not due to differences in baseline characteristics between the patients in
the Connecticut and NINDS cohorts. First, stroke severity and early changes
detected on CT images were the only factors associated with the occurrence
of intracranial hemorrhage in the NINDS trial,1, 22
and we found no significant differences in the results of admission CT scans
(eg, edema, sulcal effacement, or shift) or in the proportion of patients
with the most severe strokes (NIHSS, >20) between the 2 cohorts. In addition,
older age was not a predictor in the NINDS trial, but was a predictor of intracranial
hemorrhage in a post hoc analysis in the European Cooperative Acute Stroke
Study.23-24 Overall, our cohort
was similar in age to patients included in the NINDS trial.
Second, if stroke severity, but not protocol violations, were associated
with adverse events, then examination of outcomes within stroke severity strata
should demonstrate no difference between patients with and those without protocol
deviations. Despite our finding that more of the patients with major protocol
violations were in the category of highest stroke severity, we also found
that within every stroke severity stratum, the in-hospital mortality rate
was the same or greater for patients with major protocol deviations compared
with patients without major protocol deviations.
MEDICIAL ERRORS
We found that the medical errors leading to protocol deviations occurred
throughout the patient care path, including initial screening questions and
laboratory testing (eg, treatment of patients with active bleeding or bleeding
diathesis), diagnostic imaging (eg, misinterpretation of CT findings), administration
of medication (eg, overdosing), and posttreatment care (eg, mismanagement
of blood pressure).
Some physicians gave tPA outside of the recommended guidelines. In 17
cases, the treating clinician documented that tPA was being given outside
of recommended guidelines. In other cases, physicians might have been aware
that guidelines were not being followed, but did not document this awareness.
In most cases, however, it appeared that the deviations in care represented
errors in the application of tPA therapy. This finding is consistent with
reports documenting a lack of experience and knowledge about thrombolytic
therapy among physicians.14-15
Clinical guidelines and treatment recommendations may not be followed
for a variety of reasons.25 This problem is
not unique to stroke, and lessons can be learned from other vascular, neurological,
and acute diseases. Because a small number of trials have been documented,
and because the recommendations are based on a pair of nearly identical trials,
a high degree of uniformity exists in the guidelines for thrombolytic therapy
for stroke. Despite this, most patients were treated outside of the guideline
recommendations.
IMPLICATIONS FOR THE USE OF THROMBOLYTIC THERAPY
The absolute increases in favorable outcomes in the NINDS trial of 11%
and 13%1 must be weighed against the higher
adverse events rates seen in clinical practice when patients are treated with
protocol deviations. The increased mortality rate found in routine practice
(12% absolute increase in mortality, from 13% to 25% overall; or 18% absolute
increase in mortality, from 13% to 31%, for patients with major protocol deviations),
even without consideration of the excess hemorrhages, likely negates the overall
benefit of tPA therapy. However, since we found no increase in mortality for
patients treated without major protocol violations, patients treated according
to guidelines should receive benefit from thrombolysis.
Our report also suggests that the frequency of the use of thrombolytic
therapy for stroke is low. In a state where approximately 6500 hospital admissions
for stroke or transient ischemic attacks occur each year, we found 63 cases
during the 18-month study period. Therefore, the thrombolytic therapy was
used in approximately 0.6% of all stroke admissions in the state. Although
we could not determine the number of ideal candidates for thrombolysis or
what proportion of ideal patients were treated, the rate of patients treated
in participating hospitals or across the state as a whole appears to be less
than that in reports from other communities. In cities and regions that have
adopted aggressive community and hospital efforts, the rates of use are higher
by an order of magnitude.5
LIMITATIONS
The retrospective nature of this study permitted us to evaluate clinical
practices without altering physicians' behavior. Our retrospective study design
has limitations, and we faced important challenges to ensure that these data
accurately described the care provided to patients in routine clinical practice.
For example, we needed to identify potentially eligible cases. Concern has
been raised about the use of codes for ischemic stroke from the International Classification of Diseases, Ninth Revision, Clinical Modification,26 but patients receiving thrombolytic
therapy for acute stroke seem likely to be recognized and to receive a code
with a stroke diagnosis. Because tPA is given to a small percentage of stroke
patients, and because administrative coding practices vary, we used multiple
case-finding methods that took advantage of local expertise when possible.
We also needed to demonstrate that our abstraction process was accurate and
reliable. Therefore, this study was based on a comprehensive medical record
review in which 2 authors abstracted the data. Since these authors were aware
of the research objectives, they used standardized definitions and procedures
to ensure accurate data abstraction. Double-entry techniques were used to
improve the reliability of data processing. Previous medical record reviews
have been shown to be effective for quality enhancement projects.27
CONCLUSIONS
Our report is a comprehensive evaluation of thrombolytic therapy for
acute ischemic stroke in routine clinical practice, and we found that the
overall rates of hemorrhage and mortality were higher than expected, given
the published randomized control trial results. An aggressive approach to
acute stroke therapy can be justified,28 and
our results demonstrate the importance of adhering to treatment guidelines,
since patients who were treated without major protocol deviations had rates
of adverse events similar to the accepted standard (the NINDS trial). Systems
should be put in place that ensure the identification of all eligible patients
and the appropriate treatment of patients in a timely manner, including measures
that guarantee that physicians have the necessary information to promote the
optimal care of patients with acute stroke. It took more than a decade for
organized systems of care to be instituted for myocardial infarction and trauma
due to motor vehicle crashes, and subsequently for patient outcomes to improve.29 The results of our study offer a point of departure
for strengthening this process for stroke care.
AUTHOR INFORMATION
Accepted for publication January 17, 2002.
This study was supported by the Charles E. Culpeper Foundation Biomedical
Pilot Initiative, New York, NY; the Yale Robert Wood Johnson Clinical Scholars
Program, Little Rock, Ark (Dr Bravata); and Career Development Awards from
the Department of Veterans Affairs Health Services Research & Development
Service, New Haven, Conn (Drs Bravata and Concato).
Corresponding author and reprints: Dawn M. Bravata, MD, Robert Wood
Johnson Clinical Scholars Program, Yale University School of Medicine, 333
Cedar St, Room IE-61 SHM, PO Box 208025, New Haven, CT 06520-8025 (e-mail: dawn.bravata{at}yale.edu).
From the Departments of Internal Medicine (Drs Bravata, Kim, and Concato),
Cardiology (Dr Krumholz), and Neurology (Dr Brass), Yale University School
of Medicine, New Haven, Conn, and the Veterans Affairs Connecticut Healthcare
System (Drs Bravata, Concato and Brass), West Haven.
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