From the American College of Emergency Physicians Clinical
Policies Subcommittee (Writing Committee) on Use of Intravenous tPA for
Ischemic Stroke: Michael D. Brown, MD, MSc (Subcommittee Chair) John H. Burton,
MD Devorah J. Nazarian, MD Susan B. Promes, MD, MBA
ABSTRACT
This clinical policy
from the American College of Emergency Physicians is the revision of a clinical
policy approved in 2012 addressing critical questions in the evaluation and
management of patients with acute ischemic stroke.1 A writing subcommittee
conducted a systematic review of the literature to derive evidence-based
recommendations to answer the following clinical questions: (1) Is intravenous
tissue plasminogen activator safe and effective for patients with acute ischemic
stroke if given within 3 hours of symptom onset? (2) Is intravenous tissue plasminogen
activator safe and effective for patients with acute ischemic stroke treated
between 3 to 4.5 hours after symptom onset? Evidence was graded and
recommendations were made according to the strength of the available data.
INTRODUCTION
Stroke is a leading cause of death in the United States,
with approximately 800,000 new strokes documented each year.2,3 Among
survivors, stroke often results in disability, reducing mobility in half of
those aged 65 years or older.2 In 1996, the Food and Drug Administration
approved intravenous (IV) tissue plasminogen activator (tPA) as a treatment for
acute ischemic stroke. Despite their approval, the use of IV tPA for stroke has
been polarizing4 and continues to generate a large volume of published
literature. The last American College of Emergency Physicians (ACEP) clinical
policy addressing the use of IV tPA for acute ischemic stroke was approved in
2012.1 Since then, changes to the ACEP clinical policies development process
have been implemented (ACEP’s clinical policy development process can be found
at http://www.acep.org/ clinicalpolicies), the grading forms used to rate
published research have continued to evolve, and newer research articles have
been published. The 2012 IV tPA clinical policy recommendation to “offer” tPA
to patients presenting with acute ischemic stroke within 3 hours of symptom
onset was consistent with other national guidelines (eg, those of the American
Heart Association5 and the American College of Chest Physicians6 ).
Unfortunately, the committee’s intent in using the term “offer” may not have
conveyed the importance of having a discussion with the patient or family about
the potential benefits and harms of IV tPA; therefore, we have expanded on this
concept with recommendations addressing shared decision making. As in the
previous ACEP clinical policy,1 the 2 critical questions addressed in this
clinical policy are: (1) Is IV tPA safe and effective for patients with acute
ischemic stroke if given within 3 hours of symptom onset? (2) Is IV tPA safe
and effective for patients with acute ischemic stroke treated between 3 to 4.5
hours after symptom onset?/
METHODOLOGY
This clinical policy was created after careful review and
critical analyses of the medical literature and was based on a systematic
review of the literature. Searches of MEDLINE, MEDLINE InProcess and other
nonindexed citations portion of MEDLINE, and the Cochrane Database were
performed. All searches were limited to English-language sources, human
studies, and adults, from January 2011 to September 2014; searches were
conducted on January 27, 2014, and September 3, 2014. Specific key
words/phrases and years used in the searches are identified under each critical
question.
Study Selection: 1,765 references were identified in the updated
literature search as potentially relevant to the critical questions (992 in the
search on January 27, 2014, and 773 in the search on September 3, 2014). From
these, 136 articles were selected from the January 27, 2014 search, and 59
articles from the September 3, 2014 search, resulting in a total of 195 new
articles for full-text review.
Additionally, given recent changes to the ACEP
clinical policy development process, articles rated as Class I or II in the
2012 policy1 were also reviewed and graded by the committee methodologists
using current grading forms (available at http://acep.org/clinicalpolicies).
Finally, relevant articles from the bibliographies of included studies and more
recent articles identified by committee members and reviewers were also
included. This policy is a product of the ACEP clinical policy development
process and is based on the existing literature; when literature was not
available, consensus of emergency physicians was used. Clinical policies are
scheduled for revision every 3 years; however, interim reviews such as this
revision are conducted when technology, methodology, or the practice
environment changes significantly. ACEP was the funding source for this
clinical policy.
Assessment of Classes of Evidence All articles used in the
formulation of this clinical policy were graded by at least 2 committee members
or methodologists; all Class I and Class II articles were graded by at least 2 methodologists.
Each article was assigned a design class with design 1 representing the
strongest study design and subsequent design classes (eg, design 2, design 3)
representing respectively weaker study designs for therapeutic, diagnostic, or
prognostic clinical reports, or meta-analyses (Appendix A). Articles were then
graded on dimensions related to the study’s methodological features, such as
randomization processes, blinding, allocation concealment, methods of data
collection, outcome measures and their assessment, selection and
misclassification biases, sample size, and generalizability. Using a
predetermined process related to the study’s design, methodological quality,
and applicability to the critical question, articles received a final Class of Evidence
grade (ie, Class I, Class II, Class III, or Class X) (Appendix B). Articles
identified with fatal flaws or that were ultimately not applicable to the
critical question received a Class of Evidence grade “X” and were not used in
formulating recommendations for this policy. Grading was done with respect to
the specific critical questions; thus, the level of evidence for any one study
may vary according to the question for which it is being considered. As such,
it was possible for a single article to receive different Classes of Evidence
as different critical questions were answered from the same study.
Question-specific Classes of Evidence grading can be found in the Evidentiary
Table (available online at www.annemergmed.com).
Translation of Classes of
Evidence to Recommendation Levels Strength of recommendations regarding each
critical question were made by subcommittee members using results from strength
of evidence grading, expert opinion, and consensus among subcommittee members
according to the following guidelines:
Level A recommendations. Generally
accepted principles for patient care that reflect a high degree of clinical
certainty (ie, based on evidence from 1 or more Class of Evidence I or multiple
Class of Evidence II studies).
Level B recommendations. Recommendations for
patient care that may identify a particular strategy or range of strategies
that reflect moderate clinical certainty (ie, based on evidence from 1 or more
Class of Evidence II studies or strong consensus of Class of Evidence III
studies).
Level C recommendations. Recommendations for patient care that are
based on evidence from Class of Evidence III studies or, in the absence of any
adequate published literature, based on expert consensus. In instances where
consensus recommendations are made, “consensus” is placed in parentheses at the
end of the recommendation.
There are certain circumstances in which the
recommendations stemming from a body of evidence should not be rated as highly
as the individual studies on which they are based. Factors such as
heterogeneity of results, uncertainty about effect magnitude and consequences,
and publication bias, among others, might lead to such a downgrading of
recommendations.
For this policy, recommendations for question 1 were based on
1 Class I randomized controlled trial, 5 Class II articles, and 29 Class III
studies. For question 2, recommendations were based on 1 Class II randomized
controlled trial and 42 Class III studies. When possible, clinically oriented
statistics (eg, likelihood ratios, number needed to treat [NNT]) are presented
to help the reader better understand how the results may be applied to the
individual patient. For a definition of these statistical concepts, see
Appendix C. This policy is not intended to be a complete manual on the
evaluation and management of patients with acute ischemic stroke but rather a
focused examination of critical issues that have particular relevance to the
current practice of emergency medicine. It is the goal of the Clinical Policies
Committee to provide an evidence-based recommendation when the medical
literature provides enough quality information to answer a critical question.
When the medical literature does not contain adequate empirical data to answer
a critical question, the members of the Clinical Policies Committee believe
that it is equally important to alert emergency physicians to this fact. This
clinical policy is not intended to represent a legal standard of care for
emergency physicians. Recommendations offered in this policy are not intended
to represent the only diagnostic or management options available to the
emergency physician. ACEP recognizes the importance of the individual
physician’s judgment and patient preferences. This guideline defines for the
physician those strategies for which medical literature exists to provide
support for answers to the critical questions addressed in this policy.
Scope
of Application. This guideline is intended for physicians working in emergency
departments (EDs).
Inclusion Criteria. This guideline is intended for adult
patients aged 18 years and older presenting to the ED with acute ischemic
stroke.
Exclusion Criteria. This guideline is not intended to be used for
pediatric or pregnant patients. A summary of potential benefits and harms of implementing
the recommendations is presented in Appendix D.
CRITICAL QUESTIONS
1. Is IV tPA safe and effective for patients with acute ischemic stroke if given within 3 hours of symptom onset?
Patient Management Recommendations Level A recommendations. None specified. Level B recommendations. With a goal to improve functional outcomes, IV tPA should be offered and may be given to selected patients with acute ischemic stroke within 3 hours after symptom onset at institutions where systems are in place to safely administer the medication. The increased risk of symptomatic intracerebral hemorrhage (sICH) should be considered when deciding whether to administer IV tPA to patients with acute ischemic stroke. Level C recommendations. When feasible, shared decisionmaking between the patient (and/or his or her surrogate) and a member of the health care team should include a discussion of potential benefits and harms prior to the decision whether to administer IV tPA for acute ischemic stroke. (Consensus recommendation).
1. Is IV tPA safe and effective for patients with acute ischemic stroke if given within 3 hours of symptom onset?
Patient Management Recommendations Level A recommendations. None specified. Level B recommendations. With a goal to improve functional outcomes, IV tPA should be offered and may be given to selected patients with acute ischemic stroke within 3 hours after symptom onset at institutions where systems are in place to safely administer the medication. The increased risk of symptomatic intracerebral hemorrhage (sICH) should be considered when deciding whether to administer IV tPA to patients with acute ischemic stroke. Level C recommendations. When feasible, shared decisionmaking between the patient (and/or his or her surrogate) and a member of the health care team should include a discussion of potential benefits and harms prior to the decision whether to administer IV tPA for acute ischemic stroke. (Consensus recommendation).
 |
| Table 1 |
Key words/phrases for literature searches:
stroke, cerebrovascular accident, thrombolytic, tPA, thrombolytic therapy, drug
therapy, emergency department or emergency room, emergency service, hospital,
and variations and combinations of the key words/phrases. A study was
considered directly applicable if IV tPA was administered within the specified
timeframe (ie, within 3 hours of symptom onset). To be included, articles were
required to report patient-centered outcomes such as sICH, mortality, or a
validated measure for functional outcome. In terms of assessing the potential
benefits of IV tPA, the subcommittee focused on the modified Rankin Scale (mRS)
because it is both patient centered and consistently reported1,7 (Table). An
“excellent” functional outcome is typically equated to a score of 0 to 1 on the
mRS; a score of 2 is considered a “good” functional outcome; and a score of 3
to 6 is considered “poor” functional outcome. To place this into context, an
mRS score of 2 is defined as a slight disability that allows the patient to
look after their affairs without assistance yet be unable to perform some
previous activities (eg, drive a car, dance).7 The major harm associated with
IV tPA therapy in this clinical setting is sICH, defined as bleeding associated
with “any decline in neurological status” per the National Institute of
Neurological Disorders and Stroke (NINDS) trials8 and, when it occurs, sICH is
ultimately associated with a substantial increase in the risk of an unfavorable
outcome (mRS score 3 to 6).9 Studies have used various definitions for sICH,
such as those requiring a deterioration of 4 or more points on the National
Institutes of Health Stroke Scale (NIHSS)9 (Figure 1). When possible, the
subcommittee reported results using the more inclusive NINDS definition.
Potential Benefits It has been nearly 20 years since the last patient was
enrolled in part 2 of the tPA for acute stroke trials sponsored by the NINDS.
This trial provided the scientific basis for the Food and Drug Administration’s
approval of the use of IV tPA in acute stroke.8 The results of the NINDS trial
(part 2) (Class I) demonstrated an absolute difference of 13% with respect to
excellent functional outcomes (ie, 39% with mRS score 0 to 1 for tPA versus 26%
for control), thus rendering a NNT of 8; 95% confidence interval [CI] 4 to 31.
Although the enrollment criteria for the NINDS trials (Figure 2) required a measurable deficit on the NIHSS, there was a paucity of patients presenting with mild stroke (NIHSS score 0 to 4).10 In an effort to address the current state of equipoise for IV tPA in patients presenting with mild (NIHSS score 0 to 4) or rapidly improving symptoms, a randomized controlled trial is actively enrolling subjects.11 Data from the NINDS trials continue to be reanalyzed and despite inherent problems with post hoc reanalyses,12 these studies highlight the strengths and limitations of the NINDS trials.10,13-19 Although strict randomization was followed in the NINDS trials, there was an imbalance in baseline stroke severity scores between the intervention and control groups.13,14 A subsequent reanalysis of the original NINDS data set showed that a larger proportion of patients with milder strokes with an NIHSS score of 0 to 5 (19% versus 4%) at 91 to 180 minutes were randomized to tPA.14 Last, the NINDS trials were designed to enroll half of their subjects within 90 minutes of symptom onset, which has raised questions about the generalizability of their findings.20 The only other randomized controlled trial (Class II) that directly addressed the critical question enrolled subjects within 6 hours of stroke symptom onset, using block randomization stratified by 0 to less than 3 hours and 3 to 6 hours.22 This study did not show benefit for tPA administered within 6 hours of symptom onset (the primary analysis), and the difference in the subgroup randomized to less than 3 hours (42% with mRS score 0 to 2 for tPA versus 38% for placebo) did not reach statistical significance (odds ratio [OR]¼1.2; 95% CI 0.6 to 2.3). A Class III open-label clinical trial, the Third International Stroke Trial (IST-3), by Sandercock et al,23 enrolled patients within 6 hours of symptom onset. In this trial, patients did not meet the standard European Union license–approved protocol for IV tPA; a large percentage of patients were elderly (53% older than 80 years), had elevated systolic blood pressure (34% greater than 165 mm Hg), or had low baseline NIHSS scores (20% with scores 0 to 5). Because of slow enrollment, the trial was stopped early.
Although the enrollment criteria for the NINDS trials (Figure 2) required a measurable deficit on the NIHSS, there was a paucity of patients presenting with mild stroke (NIHSS score 0 to 4).10 In an effort to address the current state of equipoise for IV tPA in patients presenting with mild (NIHSS score 0 to 4) or rapidly improving symptoms, a randomized controlled trial is actively enrolling subjects.11 Data from the NINDS trials continue to be reanalyzed and despite inherent problems with post hoc reanalyses,12 these studies highlight the strengths and limitations of the NINDS trials.10,13-19 Although strict randomization was followed in the NINDS trials, there was an imbalance in baseline stroke severity scores between the intervention and control groups.13,14 A subsequent reanalysis of the original NINDS data set showed that a larger proportion of patients with milder strokes with an NIHSS score of 0 to 5 (19% versus 4%) at 91 to 180 minutes were randomized to tPA.14 Last, the NINDS trials were designed to enroll half of their subjects within 90 minutes of symptom onset, which has raised questions about the generalizability of their findings.20 The only other randomized controlled trial (Class II) that directly addressed the critical question enrolled subjects within 6 hours of stroke symptom onset, using block randomization stratified by 0 to less than 3 hours and 3 to 6 hours.22 This study did not show benefit for tPA administered within 6 hours of symptom onset (the primary analysis), and the difference in the subgroup randomized to less than 3 hours (42% with mRS score 0 to 2 for tPA versus 38% for placebo) did not reach statistical significance (odds ratio [OR]¼1.2; 95% CI 0.6 to 2.3). A Class III open-label clinical trial, the Third International Stroke Trial (IST-3), by Sandercock et al,23 enrolled patients within 6 hours of symptom onset. In this trial, patients did not meet the standard European Union license–approved protocol for IV tPA; a large percentage of patients were elderly (53% older than 80 years), had elevated systolic blood pressure (34% greater than 165 mm Hg), or had low baseline NIHSS scores (20% with scores 0 to 5). Because of slow enrollment, the trial was stopped early.
 |
| Figure 1 |
Among the prespecified subgroups of subjects
randomized at less than 3 hours of symptom onset (N¼849), the tPA group
achieved better functional outcomes compared with controls (31% with good
functional outcomes for tPA versus 23% for controls; OR¼1.64; 95% CI 1.03 to
2.62), resulting in a NNT of 13 (95% CI 7 to 51). The literature search also
identified an updated metaanalysis (Class II) of randomized controlled trials
for IV tPA.24 The pooled results of the prespecified subgroup analysis for
treatment within 3 hours demonstrated benefit in terms of a good functional
outcome (mRS score 0 to 2) with thrombolysis (OR¼1.53; 95% CI 1.26 to 1.86).
Although the authors of the meta-analysis concluded that the 12 studies analyzed
were at low risk of bias, a sensitivity analysis based on the methodological
and quality differences was not performed. The trial contributing the largest
proportion of patient data to the pooled estimate of effect (ie, Sandercock et
al IST-323) was rated Class III by the subcommittee. Another meta-analysis
(Class III) based on individual patient-level data reported a similar effect
size for tPA administered within 3 hours of symptom onset (OR¼1.75; 95% CI 1.35
to 2.27).25 Although efficacy estimates in observational studies are often
flawed, these studies may provide information on safety.
Among the many
registry studies identified in the updated searches, methodological limitations
such as selection bias (eg, eligible patients missed or purposely not enrolled
in a registry) and measurement bias (eg, mRS score assessed by research
assistant telephone follow-up rather than an in-person interview by a
neurologist) typically resulted in downgrading to Class III or Class X. The
search identified a few randomized controlled trials comparing new
interventions to standard IV tPA (serving as the control group), which provided
data on safety and functional outcomes similar to that of prospective cohort
studies. In summary, numerous Class III studies report prevalences of excellent
functional outcomes (mRS score 0 to 1) with administration of IV tPA within 3
hours of symptom onset ranging from 37% to 53%.26-36 However, registries
typically included patients with less severe strokes (baseline mean or median
NIHSS scores ranging from 11 to 13) compared with those enrolled in the NINDS
trials.
Potential Harms
The NINDS trial, part 28 (Class I) demonstrated an
absolute increase in the prevalence of sICH of 6% (ie, sICH¼7% for tPA versus
1% for control), thus indicating a number needed to harm [NNH] of 17; 95% CI 12
to 34. The Class II meta-analysis by Wardlaw et al24 reported a pooled estimate
for sICH of 8% for tPA versus 1% for controls (OR¼4.55; 95% CI 2.92 to 7.09);
however, the definition for sICH varied among the included individual trials.
Among Class III cohort studies, prevalences of sICH were remarkably consistent
when based on the NINDS definition (approximately 5% to 7%).33,35-44 As
expected, reported rates of sICH are lower in studies that used standard doses
of tPA and a definition requiring a deterioration of 4 or more points on the
NIHSS (range of 4% to 6% for sICH).28,30,31,39,45-49 In the NINDS trials,8
there was no statistically significant difference in 3-month mortality (17% for
tPA versus 21% for control; OR¼0.81; 95% CI 0.54 to 1.21). Similarly, 1 Class
II and 1 Class III meta-analyses reported no difference in mortality for
patients treated with IV tPA within 3 hours of symptom onset to the end of
follow-up: Wardlaw et al24 (OR¼0.91; 95% CI 0.73 to 1.13) and Emberson et al25
(OR¼1.00; 95% CI 0.81 to 1.24), respectively. According to another Class III
meta-analysis by Wardlaw et al50 that included trials using tPA and other
thrombolytic agents, there was again no difference in mortality when given within
3 hours of stroke onset (OR 0.99; 95% CI 0.82 to 1.21). Among the Class III
cohort studies, there was substantial variability in the reported mortality
prevalences, ranging from 1% to 24%.27-31,33-37,40,45,51 Appendix D contains
information on key risk-benefit concepts.
2. IV tPA safe and effective for patients with acute ischemic stroke treated between 3 to 4.5 hours after symptom onset?
Patient Management Recommendations
Level A recommendations. None specified.
Level A recommendations. None specified.
Level B recommendations. Despite the known risk of sICH and the
variability in the degree of benefit in functional outcomes, IV tPA may be
offered and may be given to carefully selected patients with acute ischemic
stroke within 3 to 4.5 hours after symptom onset at institutions where systems are
in place to safely administer the medication.
Level C recommendations. When
feasible, shared decisionmaking between the patient (and/or his or her
surrogate) and a member of the health care team should include a discussion of
potential benefits and harms prior to the decision whether to administer IV tPA
for acute ischemic stroke. (Consensus recommendation)
Key words/phrases for literature searches: stroke, cerebrovascular accident, thrombolytic, tPA, Thrombolytic therapy, drug therapy, emergency department or emergency room, emergency service, hospital, and variations and combinations of the key words/phrases.
Potential Benefits The Class II study, European Cooperative
Acute Stroke Study (ECASS III) (Figure 2), by Hacke et al21 demonstrated
improvement in the prevalence of excellent functional outcomes (mRS score 0 to
1) with IV tPA administered within 3 to 4.5 hours after symptom onset (52% for
tPA versus 45% for controls; OR¼1.34; 95% CI 1.02 to 1.76; NNT¼14; 95% CI 7 to
244). Reasons for downgrading ECASS III to a Class II level include baseline
differences between groups and changes in the timing of tPA administration
during the course of the study. The Class III open-label clinical trial (IST-3)
by Sandercock et al23 enrolled patients not meeting the standard European
Union–approved protocol for IV tPA as discussed under critical question 1
above. In the 3- to
4.5-hour subgroup (N¼1,177), there was no statistically
significant difference in functional outcomes in those randomized to the tPA
arm (32% with good functional outcome in the tPA group versus 38% in the
control group [OR¼0.73; 99% CI 0.50 to 1.07]).
 |
| Figure 2 |
The investigators reported this
outcome using a 99% CI rather than a conventional 95% CI; use of a 95% CI would
have resulted in a statistically significant association between patients in
the placebo arm and good functional outcomes. An older Class III randomized
trial also showed no difference in 90-day functional outcomes between the tPA
and control groups.52 A Class III meta-analysis by the Stroke Thrombolysis
Trialists’ Collaborative Group25 that pooled individual patient data from
multiple trials reported an effect size similar to that of ECASS III (OR¼1.26;
95% CI 1.05 to 1.51) for the 3- to 4.5-hour subgroup. Among the Class III
observational studies, there was wide variability in baseline stroke severity
(mean NIHSS scores ranged from 5 to 17), making comparisons
difficult.33,36,37,39,53-67
Potential Harms
The Class II study by Hacke et al21
reported sICH prevalence of 8% for tPA versus 4% for placebo (OR¼2.38; 95% CI
1.25 to 4.52; NNH¼23; 95% CI 13 to 78); there was no difference in mortality
between the 2 groups. The Class III individual patient data meta-analysis also
reported no difference in mortality for the 3- to 4.5-hour subgroup (hazard
ratio¼1.14; 95% CI 0.95 to 1.36).25 Among other Class III
studies,33,36,37,41,44,50,55,56,58,61,66,68-77 the prevalences of sICH
associated with IV tPA administration within 4.5 hours ranged from 3% to 8%
when based on the NINDS definition, whereas the prevalence was lower (2% to 6%)
for those studies using an sICH definition requiring a change of 4 or more on
the NIHSS.39,53,54,57,60,62-65,67,78-84
Future Research
Further research is
needed to refine estimates for the effectiveness and safety of IV tPA across
the entire acute stroke population (ie, heterogeneity of treatment effect) so that
clinicians and patients can have a more informed conversation about who is most
likely to benefit from the administration of IV tPA, and clinicians can better
identify those individuals at highest risk for sICH and other
complications.85-89 There is some evidence to suggest that lower weight-based
doses of tPA may be effective and result in fewer adverse outcomes, warranting
further studies in this area.26,75,82,90 Advancement in precision medicine (eg,
predicting risk based on systems biology) and more accurate assessment of
patient weight may play a role in deciphering the appropriate treatment of
stroke patients. Although trial results on endovascular interventions have been
mixed,78,91,92 more recent trials focusing on the subgroup of patients with
large vessel occlusion have reported benefit,83,84,93,94 thus representing an
area of research that is likely to yield further improvements in acute stroke
care. Relevant industry relationships: There were no relevant industry
relationships disclosed by the subcommittee members. Relevant industry
relationships are those relationships with companies associated with products
or services that significantly impact the specific aspect of disease addressed
in the critical question.
 |
| Appendix A: Literature classification schema. |
 |
| Appendix B: Approach to downgrading strength of evidence. |
 |
| Appendix C: Likelihood ratios and number needed to treat. |
Appendix D. Potential benefits and harms of implementing the
recommendations
1. Is IV tPA safe and effective for patients with acute
ischemic stroke if given within 3 hours of symptom onset? Patient Management
Recommendations
Level A recommendations. None specified.
Level B
recommendations. With a goal to improve functional outcomes, IV tPA should be
offered and may be given to selected patients with acute ischemic stroke within
3 hours after symptom onset at institutions where systems are in place to
safely administer the medication. The increased risk of sICH should be
considered when deciding whether to administer IV tPA to patients with acute
ischemic stroke.
Level C recommendations. When feasible, shared decisionmaking
between the patient (and/or his or her surrogate) and a member of the health
care team should include a discussion of potential benefits and harms prior to
the decision whether to administer IV tPA for acute ischemic stroke. (Consensus
recommendation)
Potential Benefit of Implementing the Recommendations:
Administration of IV tPA within 3 hours of stroke symptom onset increases the
probability of better long-term functional outcome (NNT¼8; 95% CI 4 to 31 when
based on data from the Class I NINDS8 trial part 2).
Potential Harm of
Implementing the Recommendations: Administration of IV tPA within 3 hours of
stroke symptom onset increases the risk of early sICH (NNH¼17; 95% CI 12 to 34
when based on data from the Class I NINDS8 trial part 2). When considering
administration of IV tPA for a patient with acute ischemic stroke within 3
hours of stroke symptom onset, the physician and patient (and/or the surrogate)
should weigh the potential benefit in terms of long-term functional outcome against
the increased risk of sICH while recognizing that IV tPA does not alter 90-day
mortality. Shared decisionmaking relies on a combination of the best available
research evidence, the clinical expertise of the providers, and the unique
attributes of the patient and the patient’s family.95-97 Patients tend to
overestimate the benefits and underestimate the harms associated with medical
interventions98; therefore, it is suggested that patient decision aids be used
to improve decision quality.95 Graphic risk communication tools such as person
icon arrays have been developed for IV thrombolysis decisions in acute ischemic
stroke.99,100 Although these tools rely on group-level data from clinical
trials rather than providing dynamic individualized estimates of risk, they may
provide a starting point for shared decisionmaking. 2. Is IV tPA safe and
effective for patients with acute ischemic stroke treated between 3 to 4.5
hours after symptom onset? Patient Management Recommendations Level A
recommendations. None specified. Level B recommendations. Despite the known
risk of sICH and the variability in the degree of benefit in functional
outcomes, IV tPA may be offered and may be given to carefully selected patients
with acute ischemic stroke within 3 to 4.5 hours after symptom onset at
institutions where systems are in place to safely administer the medication.
Level C recommendations.
When feasible, shared decisionmaking between the patient (and/or his or her surrogate) and a member of the health care team should include a discussion of potential benefits and harms prior to the decision whether to administer IV tPA for acute ischemic stroke. (Consensus recommendation) Potential Benefit of Implementing the Recommendations: Administration of IV tPA for patients with ischemic stroke within 3 to 4.5 hours of stroke symptom onset may increase the probability of better longterm functional outcome (NNT¼14; 95% CI 7 to 244 when based on data from the Class II ECASS III21 trial). Potential Harm of Implementing the Recommendations: Administration of IV tPA for patients with ischemic stroke within 3 to 4.5 hours of stroke symptom onset increases the risk of early sICH (NNH¼23; 95% CI 13 to 78 when based on data from the Class II ECASS III21 trial). When considering administration of IV tPA for a patient with ischemic stroke within 3 to 4.5 hours of stroke symptom onset, the physician and patient (and/or the surrogate) should weigh the potential benefit in terms of long-term functional outcome against the increased risk of sICH.
Evidentiary Tables and References: http://www.acep.org/workarea/
Virtual Journal Club October 2015 Questions:
When feasible, shared decisionmaking between the patient (and/or his or her surrogate) and a member of the health care team should include a discussion of potential benefits and harms prior to the decision whether to administer IV tPA for acute ischemic stroke. (Consensus recommendation) Potential Benefit of Implementing the Recommendations: Administration of IV tPA for patients with ischemic stroke within 3 to 4.5 hours of stroke symptom onset may increase the probability of better longterm functional outcome (NNT¼14; 95% CI 7 to 244 when based on data from the Class II ECASS III21 trial). Potential Harm of Implementing the Recommendations: Administration of IV tPA for patients with ischemic stroke within 3 to 4.5 hours of stroke symptom onset increases the risk of early sICH (NNH¼23; 95% CI 13 to 78 when based on data from the Class II ECASS III21 trial). When considering administration of IV tPA for a patient with ischemic stroke within 3 to 4.5 hours of stroke symptom onset, the physician and patient (and/or the surrogate) should weigh the potential benefit in terms of long-term functional outcome against the increased risk of sICH.
Evidentiary Tables and References: http://www.acep.org/workarea/
Virtual Journal Club October 2015 Questions:
1. The 2015 ACEP Clinical Policy regarding the use of Intravenous Tissue Plasminogen Activator for the Management of Acute Ischemic stroke was approved/endorsed by:
- The American College of Emergency Physicians
- The American Academy of Neurology
- The Emergency Nurses Association
- a and c
2. Level ___ recommendation is defined as: “Generally accepted principles for patient care that reflect a high degree of clinical certainty (ie, based on evidence from 1 or more Class of Evidence I or multiple Class of Evidence II studies).”
a. A
b. B
c. C
d. D
3. The 2015 ACEP guidelines granted Level _____ evidence for the safety and efficacy of IV tPA within 3 hours of stroke symptom onset. The guidelines note that for these selected patients IV tPA “should be offered and ________ be given.”
- A, should
- B, may
- C, could
- D, should not
4. The 2015 ACEP guidelines granted Level _____ evidence for the safety and efficacy of IV tPA within 3-4.5 hours of stroke symptom onset. The guidelines note that for these selected patients, IV tPA “______ be offered and may be given.”
- A, should
- B. may
- C, could
- D, should not
5. True or False: In both the “under 3 hour” recommendation and the “3 to 4.5 hour” recommendation, Level C evidence was given to “shared decision making between the patient (and/or his or her surrogate) and a member of the health care team” and for “a discussion of potential benefits and harms.”
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