Anticoagulant Versus Antiplatelet Therapy for
Acute Ischaemic Stroke
Tracey L. Rutledge
BSN, University ofNorthern British Columbia, 2004

Project Submitted In Partial Fulfillment Of
The Requirements For The Degree Of
Master of Science
In
Nursing
(Family Nurse Practitioner)

The University ofNorthern British Columbia
October, 2008
© Tracey L. Rutledge, 2008

ll

Abstract
Acute ischaemic stroke is a leading cause of death in Canada and should be a priority in
health care. This paper defines acute ischaemic stroke and provides current statistics,
economic costs, risk factors, treatments, and management options. A gap between current
practice and literature is identified. Specific treatments of anticoagulant and antiplatelet
therapy are explored through systematic reviews, clinical trials, and national guidelines.
Considerable consistency in research findings have led to evidenced-based guidelines.
Implications for practice, including barriers and facilitators to incorporating evidence-based
recommendations are identified. The study concludes with an identification of the need for
clinical practice guidelines in Northern Health along with the implementation of current
provincial guidelines that will provide best patient care in treating patients with acute
ischaemic stroke.

lll

TABLE OF CONTENTS
Approval
Abstract

11

Table of Contents

lll

Acknowledgement

IV

Background
Financial Cost of Stroke
Risk Factors of Stroke
Causes of Stroke
Clinical Presentation of Stroke
Diagnosing Stroke

1

2
3
3
3

Treatment of AIS
Thrombolytics
Anitcoagulants
Anti platelets

4
4
5
6

Management of AIS

6

Study Question

7

Literature Review
Sources and Research Processes
Single Studies and Trials
Systematic Reviews
Clinical Practice Guidelines
National Guideline Clearinghouse
National Recommendations

7
7
8
9
12
13
15

Discussion

16

Implications for Practice
Canadian and British Columbia Stroke Strategies

16
17

Barriers and Facilitators

18

Implementing Evidence-Based Practice

20

Recommendations

20

Conclusion

21

References

22

Appendix A - Hallmarks of a Credible Guideline

26

Appendix B - Criteria for Reporting Clinical Practice Guidelines

27

2

IV

Acknowledgement
I would like to acknowledge Martha MacLeod and Amy Klepetar of the University of
Northern British Columbia for their direction in preparing this project. I would also like to
acknowledge my wonderful family and dear friends for the support, encouragement, and time
that they have given me to work on the Master ofNursing Programme.

1

Anticoagulant Versus Antiplatelet Therapy for Acute Ischaemic Stroke
Acute ischaemic stroke (AIS) is a leading cause of death in Canada and should be a
priority in health care. This paper defines AIS and provides current statistics, economic costs,
risk factors, treatment and management options. A gap between current practice and
literature is identified, and the efficacy of anticoagulant and anti platelet therapy are
determined through systematic reviews, clinical trials, and national guidelines.
Background
Cerebrovascular disease is a frequently occurring neurologic disorder that is
characterized by the sudden loss of circulation to an area of the brain (Becker, 2006). Two
broad types of cerebrovascular disease resulting from brain abnormalities are hemorrhagic
and ischaemic stroke (Harrison's Practice, 2007). Diseases ofthe circulatory system
accounted for 74,824 deaths in 2001 , about 34% of the total deaths in Canada; 21 % of
disease due to the circulatory system were attributed to stroke (Statistics Canada, 2004).
Stroke is the third leading cause of death in Canada: seven percent of all deaths in Canada
are due to stroke (Heart and Stroke Foundation, 2008). Between 40,000 and 50,000
Canadians are hospitalized for strokes every year (Health Canada, 2006) and about 15,000 of
those strokes are fatal (Health Canada, 2006). According to the British Columbia Vital
Statistics Agency, six British Columbians die each day from cerebrovascular disease (2006).
British Columbia Vital Statistics Agency (2006) reports a downward trend of
cerebrovascular mortality with 409 deaths from 2001 to 2006 in the Northern Health
Authority.
According to the Heart and Stroke Foundation (2008), of the Canadians who have a
stroke, 15% will die soon after the stroke, 10% will recover completely, 25% will recover

2

with minor disability, 40% are left with moderate to severe impairment, and 10% are
severely disabled and require long-term care. Disabilities may range from slight weakness of
a hand to permanent hemiparesis. A stroke survivor has a 20% chance of restroke within two
years (Health Canada, 2006). This paper will deal specifically with AIS as it is the most
common type of stroke.
Financial Cost of Stroke
Stroke costs the Canadian economy 2.7 billion dollars per year in physician services,
hospital costs, lost wages, and lost productivity, with an average of$27,500 per stroke (Heart
and Stroke Foundation, 2008). Stroke cost in British Columbia is estimated to be greater than
$327 million annually (HSFBC&Y, 2005). Lindsay et al. (2008) contend that organized
stroke care over a 20-year period could prevent 160,000 strokes; a projected $8 billion in
savings to the Canadian health care system.
Risk Factors for Stroke
After age 55, the risk of stroke doubles every 10 years and more women than men die
from stroke at all ages (Health Canada, 2006; Heart and Stroke Foundation, 2007). Some
pre-existing medical conditions as well as some lifestyle factors can put people at a higher
risk for stroke. Risk factors for stroke include hypertension, diabetes, hyperlipidemia, atrial
fibrillation, atherosclerosis, recent myocardial infarction, family, and/or personal history of
heart disease (Harrison's Practice, 2007; Health Canada, 2006). Other risk factors include
cigarette smoking, acquired immune deficiency syndrome (AIDS), recreational drug use, and
heavy alcohol consumption (Center for Disease Control and Prevention, 2007).

3
Causes of Stroke
While hemorrhagic or 'bleeding' stroke accounts for 15-20 % of total strokes, acute
ischaemic stroke (AIS) accounts for 80-85% of all strokes. AIS is caused by emboli,
thrombus, or systemic hypoperfusion that blocks an artery leading to the brain (Granitto,
2008). Embolic causes due to atrial fibrillation, patent foramen ovale, and low ejection
fraction account for 45% of ischaemic strokes. Thrombus due to plaque buildup and
narrowed arteries accounts for 30% of ischaemic strokes. The remaining 25% of ischaemic
strokes are attributable to systemic hypoperfusion, hypercoagulable states, and cryptogenic
causes (Granitto ). With the major proportion of strokes being ischaemic, it is prudent for this
project to determine the best evidence for treating AIS .
Clinical Presentation of Stroke
The usual clinical presentation of AIS include neurologic impairment such as
transient blindness, diplopia, dizziness, headache, sensory deficiencies, speech problems,
motor difficulties, and weakness or numbness (Heart and Stroke Foundation of Canada,
2007). Severe impairment may include a loss of consciousness after the event, coma, or
death (Tierney, 2007). Generally, the greater or larger the cerebral vessel involved, the
greater the risk of morbidity and mortality.
Diagnosing Stroke
Emergency non-contrast head computed tomography (CT) is mandatory for
distinguishing ischaemic from hemorrhagic stroke. A head CT scan is a crucial diagnostic
tool in the evaluation of this cause of stroke, since patients with AIS may be eligible to
receive thrombolytics therapy, while patients with hemorrhagic stroke are best treated with a
completely different therapeutic pathway (Becker, 2006). This paper will focus on the

4

treatment of AIS with specific interest in anticoagulant and antiplatelet therapy. Treatment of
AIS with thrombolytics will be briefly discussed due to the importance of the medication in
treating AIS.
Treatment of AIS
The guiding principle in AIS treatment is the phrase Time is Brain. This refers to the
need to act quickly because brain tissue is lost with every minute that passes. Treatment of
AIS includes three different medications: thrombolytics, anticoagulants, and antiplatelets.
This paper will define the three classes of medications, however, the focus will be on
antiplatelet therapy versus anticoagulant therapy because there appears to be a considerable
discrepancy between individual practice and recommended guidelines with regard to the two
treatments.
Thrombolytics

Granitto (2008) asserts that to date, the use of intravenous tissue plasminogen
activator tPA is the sole thrombolytic agent approved for use in patients with AIS. This drug
class is commonly referred to as ' clot buster' medication and has been used since 1996.
Dissolving the clot will reduce damage to the brain, therein reducing the effects of the stroke
and decreasing permanent disability (AHA, 2008). Tierney (2007) states that tPA decreases
the risk of disability by 30% in patients who receive the drug within 3 hours of onset of AIS.
Effective and rapid treatment of AIS increases quality of life and decreases the mortality rate.
The use of tP A carries the risks of intracerebral hemorrhage and angioedema with possible
airway compromise, all which are serious and life threatening side effects (Adams et al.,
2007). TP A should therefore only be used within the confines of stroke guidelines, and
initiated only after AIS is confirmed by a head CT scan. Since ischaemic stroke must be

5

accurately diagnosed by CT scan, many patients are unable to receive the clot busting
therapy due to time constraints. The 3 hour time frame for use oftPA limits its use in rural
and remote areas of British Columbia. In addition to time, there are many inclusion criteria
that must be met for a patient with AIS to receive tP A such as medical history and current
illnesses. TP A has substantial costs including the medication itself and the specially trained
medical/nursing staff required to administer it.
Anticoagulants
Anticoagulant drug therapies include heparin, low molecular weight heparin
(LMWH), and warfarin. Warfarin reduces the synthesis of clotting factors by depleting the
body's store of vitamin K and takes 48 to 72 hours to become therapeutic (Valentine & Hull,
2008). Warfarin causes twice as many hemorrhages as aspirin, particularly in patients with a
history ofbleeding or genetic disorder and in elderly patients (Hankey, 2005). Warfarin has a
narrow therapeutic window, requires frequent dosing changes, continuous monitoring, and is
affected by numerous drug and food interactions (Hankey). Heparin and LMWH prevent
blood clotting by potentiating the action of antithrombin therein inactivating thrombin and
preventing the conversion of fibrinogen to fibrin (Valentine & Hull, 2007). While the
heparins also have a narrow therapeutic window, and require twice daily injections, the
duration of action is about 12 hours compared to 3-5 days for warfarin. However, like
warfarin, the heparins also have similar bleeding complications, which could offset any
benefits. Hemorrhagic stoke will develop if an AIS is treated with warfarin or heparin 50%
more frequently than if treated with aspirin (Berge & Sandercock, 2002).

6

Antiplatelets
Anti platelet drug therapies include aspirin and thienopyridine derivatives (clopidogrel
and ticlopidine). Aspirin, clopidogrel, and ticlopidine block prostaglandin synthetase action
which prevents formation of the platelet aggregating substance thromboxane (Lexi-Comp,
2008a; Lexi-Comp, 2008b). Aspirin has been used for centuries for medicinal purposes and
is also quite inexpensive compared to newer antiplatelet drugs. Aspirin is easy to administer
and continuous monitoring is not required for patients who receive this medication. Aspirin
is not without potential side effects, which include allergic reactions, upper gastrointestinal
upset, gastrointestinal bleeding, and rash (Hankey, 2005). However, the side effects of the
theinopyridine derivatives are greater in severity compared to those occurring with aspirin
and include hemorrhage, diarrhea, rash, and neutropenia (Hankey). Current Canadian and
American clinical practice guidelines state that anticoagulant therapy is not recommended for
AIS and that antiplatelet therapy using aspirin should be initiated immediately after
confirmation of AIS by computed tomography (CT) scan (Adams, et al, 2007; Canadian
Stroke Strategy, 2006).
Management of AIS
Physicians have used anticoagulants to treat patients with AIS for over 50 years, yet
despite its longstanding and widespread use, anticoagulant therapy is the subject of much
debate (Adams et al, 2007). Adams et al. assert that disagreements exist regarding the
usefulness of emergency anticoagulation, the best agent to administer, the preferred route of
administration, use of a bolus dose to initiate treatment, the level of anticoagulation required,
and the duration of treatment. Physicians often erroneously prescribe anticoagulants to
patients with recent stroke in an effort to prevent early recurrent stroke and to improve

7

neurological outcomes (Adams et al.). Nurse Practitioner Stroke Guidelines assert that early
anticoagulant therapy does not decrease the risk of neurological worsening (Granitto, 2008).
In the past decade, guidelines for stroke management have included
recommendations on medication use in AIS . These recommendations have changed over the
years to incorporate new research findings. Because health care providers continue to
prescribe both anticoagulant and antiplatelet therapy for AIS, the current evidence on these
therapies merits review.
Study Question
The study question explored in this project is: In patients with acute ishaemic stroke,
does antiplatelet therapy as compared to anticoagulant therapy reduce the incidence of
restroke and mortality? The patient population consists of people diagnosed with AIS. The

intervention of interest is the use of anti platelet therapy compared with anticoagulant
therapy. The outcome of interest is which group of patients has had a more positive outcome,
specifically, reduced incidence of restroke and decreased mortality.
Literature Review
Sources and Research Processes

Databases used to find evidence to address the question include: Cochrane Database
of Systematic Reviews (CDSR), National Guidelines Clearinghouse (NGC), Cumulated
Index ofNursing and Allied Health Literature (CINAHL), MEDLINE, Science Direct,
Pubmed, Ovid, Blackwell Synergy, Evidence-based Medicine (EBM) reviews, and
UpToDate. The key words used included: acute ishaemic stroke, antiplatelet, anticoagulant,
aspirin and stroke, stroke nursing care, antiplatelet$ and anticoagulant$, stroke prevention,
ishaemic stroke and study$, acute ishaemic stroke and trials, cerebrovascular accident,

8
vascular infarct, evidence and prevention, and stroke and guidelines. Inclusion criteria were
patients diagnosed with AIS and treated with either anticoagulant, antiplatelet therapy, or
combination therapy. The patients in the studies included men and women of varying
ethnicities and ages. The systematic reviews were chosen because the reviewers
independently selected studies for inclusion, assessed the quality of trials, and extracted the
data. The search resulted in three single studies and trials (a RCT, a multi-centre trial, and a
case cross-over study) totaling 4,900 patients, four systematic reviews totaling 104,160
patients, and six national guidelines for review and analysis.

Single Studies and Trials
Randomised controlled trials and observational studies provide complimentary
evidence to the more powerful systematic review (Barton, 2000). The following single
studies and trials compare anti platelet agents for the treatment of diagnosed AIS. The
antiplatelet agents included in these studies and trials are aspirin, ticlopidine, clopidogrel,
and a combination of aspirin and clopidogrel.
Grau et al. ' s, (2003) case-cross over study of 31 patients compared clopidogrel 75mg
and aspirin 300 mg each as monotherapy and as combination therapy. Patients diagnosed
with AIS and treated with aspirin for secondary prevention, received clopidogrel alone, or a
combination of clopidogrel and aspirin for four weeks. Grau, et al. found that while
combined therapy indicates a lower risk of thrombosis, it increases the risk of hemorrhage.
However, in a multi-centre trial involving 1809 African-American patients diagnosed with
stroke, within 90 days of onset, in over 60 cities, aspirin 650 mg was found to be as effective
as ticlopidine 500 mg in preventing restroke (Gorlick, 2003). The potential for serious side
effects was found in the patients receiving ticlopidine, therefore outweighing the benefits of

9

administering the medication. Hass et al. ' s ( 1989) RCT involving 3069 patients diagnosed
with recent transient or mild persistent focal cerebral or retinal ischaemia compared
ticlopidine 500 mg to aspirin 1300 mg. Hass et al. found ticlopidine to be only 2 percent
more effective than aspirin for preventing restroke or death in the following three years.
However, the study also found that the side effects ofticlopidine were doubled in
comparison to those of aspirin. Noted in this study are the large dose of aspirin and the age of
the study. While the above three studies are not as credible on their own as are systematic
reviews and national guidelines, the findings are similar to the fmdings of the more credible
evidence and are useful in the context of this paper. They were chosen for this project
because they address the pressing study question, were in peer reviewed journals, and are
examples of well done studies. Evidence from the above studies and trials clearly determines
that aspirin should be administered instead of other antiplatelet medications, however, the
question of appropriate aspirin dosage remains. While these single studies and trials are
included in systematic reviews and national guidelines, they are also valuable as evidence to
support individual health care providers as they search for evidence-based provision of care
to patients with AIS.

Systematic Reviews
Systematic reviews of randomized controlled trials are "traditionally the gold
standard for judging the benefits of treatments, mainly because it is conceptually easier to
attribute any observed effect to the treatment being compared" (Barton, 2000). In the
following four systematic reviews, one examines the use of anti platelet therapies clopidogrel
and ticlopidine compared to aspirin for the prevention of AIS . The second examines the
anticoagulant therapy of unfractionated and low molecular weight heparin compared to

10
aspirin. The third examines the anticoagulants heparinoids and warfarin compared to aspirin.
The fourth compares patients given aspirin versus no aspirin therapy.
Hankley, Sudlow, and Dunbabin's (2000) systematic review of four double blind
randomized trials included 22,656 patients diagnosed as high risk. The study compared
clopidogrel and ticlopidine versus aspirin for preventing AIS in high risk patients. High-risk
patients were defined as those identified as having TIAs or previous clinical manifestations
of disease in cerebral, coronary, or peripheral circulation systems. The average age was 63
and two thirds of the patients were men. The study sample may not be completely
generalizeable in that stroke occurs more frequently in women. Comparisons were made
between clopidogrel 75 mg, ticlopidine 250 mg, and aspirin 325 mg. The theinopyridines
were found to be slightly more effective than aspirin in preventing stroke in high risk
patients, however, the side effects of skin rash and diarrhea increased with clopidogrel (30%)
and ticlopidine (>60%). Neutropenia was seen in patients who were administered ticlopidine.
Given the cost comparison and the side effects of the theinopyridines compared to aspirin,
aspirin administration is clearly the first choice in treating patients with AIS.
Berge & Sandercock's (2002) systematic review of 16, 558 patients in four RCTs
compared unfractionated heparin (UFH) with low molecular weight heparin (LMWH).
Aspirin was used as a control in all trials however, and no specific dose of aspirin was
identified. The patients had been diagnosed with AIS by CT Scan or MRI within 48 hours of
onset of symptoms. Berge & Sandercock found that treatment with the anticoagulant heparin
was of no more value than treatment with aspirin. They noted that heparin use caused
increased bleeding complications equivalent to 20 more deaths per 1000 patients and restroke
equivalent to 10 more restrokes per 1000 patients. Berge & Sandercock contend that aspirin

11
is inexpensive, easy to use, and is the "standard" treatment for patients with AIS. This
systematic review should be recognized as one of the higher levels of evidence in the
recommendation of using aspirin instead of anticoagulant therapy based on the large number
of participants and the generalizability of the findings.
Gubitz, Sandercock & Counsell' s (2007) systematic review of23,547 patients in 22
RCTs compared the anticoagulants, unfractionated heparin, low molecular weight heparin,
and warfarin versus aspirin control groups. They found that the immediate use of lowmolecular-weight heparin, heparinoids, oral anticoagulants, and thrombin inhibitors
increased the risk of major extracranial and intracranial hemorrhages equivalent to nine
people per 1000 and prevented the equivalent of nine recurrent ischaemic strokes per 1000
patients compared to the aspirin control group. They concluded that the use of anticoagulant
therapy is not associated with short or long term benefit and is associated with an increased
risk of major intracranial and extracranial hemorrhages. Gubitz et al. found no evidence that
anticoagulant therapy reduced the odds of death from all causes at the end of follow-up (odds
ratio =1.05 , 95%; confidence interval 0.98 to 1.12). This systematic review should be
recognised as having major implications for clinical practice and stronger than the previous
2000 and 2002 systematic reviews in that it is 5-7 years newer.
Sandercock, Gubitz, Foley, & Counsell's (2007) systematic review of nine RCTs of
41,399 patients assessed the efficacy and safety of aspirin in patients diagnosed with AIS.
They found that aspirin (160 mg - 300 mg) given within 48 hours of stroke onset reduced the
risk of restroke equivalent to 7 per 1000 patients at a six month follow up compared to
patients not given aspirin. They concluded that aspirin reduces the risk of restroke without
major risk of hemorrhagic complications and improves long term outcome. Sandercock et al.

12
found that mortality was reduced equivalent to 13 patients per 1000 for patients allocated to
aspirin. This systematic review is different from the previous ones in that aspirin and aspirin
dosage is the only agent studied, most likely due to the fact that aspirin has been the
presumed treatment for AIS . Of major importance in this systematic review is the dosage of
aspirin recommended, which is a range of 160- 300 mg.
Clinical Practice Guidelines
Fletcher (2007) states that clinical practice guidelines (CPGs) are the new reality in
medicine and that CPGs are "recommendations for clinicians about the care of patients with
specific conditions .. .based on the best available research evidence and practice experience".
CPGs contain two parts, beginning with the foundation of a systematic review of the current
research evidence-based on a specific clinical question which is focused on the strength of
evidence on which clinical decision making for the particular condition is based. The second
part, "which involves both the evidence and the value judgments, is a set of
recommendations for how patients with that condition should be managed, everything else
being equal" (Fletcher). The purpose of a CPG is to guide and help the health care provider
take better care of patients. CPGs are suggestions for care, rather than rules, and there will
always be patients who require independent management. However, it is crucial to critique
and recognise credible guidelines because thousands of guidelines, which vary in quality
have been published. Fletcher states that the hallmarks for credible guidelines can be
recognized by several easily identifiable characteristics which include: expertise, evidencebased, broad-based, regency, imprimatur, implementation, and renew (Appendix A). Fletcher
also defines the criteria for reporting clinical practice guidelines (Appendix B).

13

National Guideline Clearinghouse
The National Guideline Clearinghouse (NGC) web site is maintained by the United
States Federal Agency for Healthcare Quality in conjunction with the American Medical
Association and the American Association of Health Plans. The NGC database houses
guidelines from most major medical organizations but does not include every guideline
(Fletcher, 2007). The NGC does not develop, produce, approve, or endorse the guidelines
represented on the website. All guidelines on the website "are produced under the auspices of
medical specialty societies, relevant professional associations, public or private
organizations, other government agencies, healthcare organizations or plans, and similar
entities" (NGC, 2007).
The following four guidelines from NGC state specifically the appropriate use and
dose of aspirin, and discuss other antiplatelet and anticoagulant therapies. Anderson et al.
(2007) sponsored by the Institute for Clinical Systems Improvement (ICSI) and funded by
seven insurance companies found that there is no evidence to support the use of
anticoagulant therapy for the treatment of AIS. They recommend that aspirin (160 mg- 325
mg) should be given orally, rectally or by nasogastric (NG) tube when treating patients with
confirmed AIS. Anderson, et al. recommends that patients who receive thrombolytics should
also receive aspirin 24 hours post thrombolytics to prevent restroke. Clopidogrel 75 mg
orally may be used in those who are allergic to aspirin. Anderson et al. do not support the use
of anticoagulants (heparins) for treatment of acute ishaemic stroke. While this guideline is
similar in its recommendations to the above systematic reviews, the fact that this guideline
was sponsored by 7 insurance companies make it less likely that health care providers will

14
incorporate it into their practice. As Fletcher (2007) states "clinicians as less likely to believe
in guidelines prepared by managed care organizations and insurance companies".
An earlier NCG guideline by Albers, Amarenco, Easton, Sacco, and Teal (2004),
which was sponsored by the American College of Chest Physicians - Medical Specialty
Society and funded by five insurance companies, recommends aspirin (160 mg- 325 mg) in
favour of anticoagulant therapy in patients diagnosed with AIS and aspirin (50- 325mg) in
patients with transient ischaemic attack (TIA). The authors also recommend aspirinclopidogrel combination, or clopidogrel 75 mg for patients who are intolerant of aspirin.
However, Coull et al. (2002), whose study was funded by the American Academy of
Neurology (AAN), recommend aspirin (160 mg -325 mg). They do not recommend any other
antiplatelet therapy or anticoagulant therapy for AIS. Coull, et al. recommend that patients
who have not been given thrombolytics and present within 48 hours of stroke should be
administered aspirin. Goldstein, et al.'s (2006) guideline which is supported by the
Cardiovascular Nursing Council and the Agency for Healthcare Research and Quality states
that aspirin is useful to prevent first stroke in women. Goldstein, et al. does not recommend
aspirin as prevention for the first stroke in men however, "[t]he use of aspirin is
recommended for cardiovascular (including but not specific to stroke) prophylaxis among
persons whose risk is sufficiently high for the benefits to outweigh the risks associated with
treatment". Goldstein, et al. recommend aspirin as prevention for the first stroke in women,
but does not state the dosage or the reasons supporting the recommendation. According to
Fletcher (2007), clinicians are most likely to accept recommendations from their own
specialty area and less likely to trust those from a government agency, therefore the

15
recommendation from the AAN is a major reason why physicians and Family Nurse
Practitioners could support aspirin use over other antiplatelet therapy.
National Recommendations
The American Stroke Association (ASA) is a division of the American Heart
Association and is dedicated to improving stroke prevention, treatment, and rehabilitation
therapy, research, education, advocacy, and the development of scientifically based standards
and guidelines (Acker, et al. 2007). The ASA developed a multidisciplinary Task Force that
determined that there is a fragmented approach to care which currently exists and thereby
poses significant obstacles to reducing the morbidity and mortality of stroke.
The American Heart and Stroke Association (2007) state that "anticoagulation with
the goal of preventing recurrent stroke, halting neurological worsening, or improving
outcomes" after AIS is not recommended. Adams et al. (2007) prepared the American Stroke
Association guidelines. Adams, et al. recommends administration of aspirin (325 mg) within
24-48 hours after AIS is diagnosed. Adams et al. , do not recommend clopidogrel or
clopidogrel combined with aspirin for AIS.
The Canadian Stroke Strategy (CSS) (2006) states that all ischaemic stroke patients
should be administered at least 160 mg of aspirin as a loading dose and then 50-325mg daily.
For patients treated with tP A, aspirin should be delayed until 24 hours post thrombolysis.
The Canadian Stroke Strategy does not support the use of other antiplatelet therapies unless
aspirin is contraindicated (such as allergy) . Acute aspirin therapy reduces the risk of early
restroke and long term therapy reduces the risk of ischaemic stroke, myocardial infarction,
and vascular death. The Canadian Stroke Strategy recommends against the use of
anticoagulant therapy for AIS. The American and Canadian national guidelines use multiple

16
sources of information including the Cochrane Database of systematic reviews, clinical
evidence, clinical practice guidelines, meta-analysis, case reports, and journal reviews to
make best recommendations.
Discussion
Evidence in the literature review clearly demonstrates that there is no benefit in using
anticoagulant therapy over antiplatelet therapy in AIS prevention or treatment. In fact,
anticoagulant therapy for patients with AIS is not recommended because anticoagulants
cause more harm than benefit. Aspirin 160 - 325 mg/day for patients with acute ischaemic
stroke is the evidence-based recommendation emerging from the literature. Basically, the
only clinical questions remaining are regarding the best loading does of aspirin ( 160mg or
325mg) to treat AIS, and the daily dose of aspirin (50mg or 325mg) to prevent restroke.
Implications for Practice
Best practices are not consistently applied to all people diagnosed with AIS resulting
in a significant gap between what should be done and what is actually being done to provide
quality care to Canadians (CSS). The major implication for practice within the primary
health care setting is that the use of aspirin should be the preferred for treatment and
prevention of acute ishaemic stroke and restroke. Daily aspirin can be used in primary,
secondary, and tertiary health prevention of acute ischaemic stroke. Usual daily prophylactic
dosage is 50- 325 mg depending on the patient's tolerance and the clinical situation (Gray,
2003). Best practices that include these recommendations for AIS care have been developed
and are in the process of being implemented in Canada and British Columbia.

17
Canadian and British Columbia Stroke Strategies
The Canadian Stroke Strategy (CSS) is a joint initiative of the Canadian Stroke
Network and the Heart and Stroke Foundation of Canada. The goal ofthe CSS is to help
support an integrated approach to stroke prevention, treatment, and rehabilitation in every
province and territory by 2010 (CSS, 2006). A national working group of the CSS developed
the Best Practice Recommendations for Stroke Care: 2006 using a consensus-based process
and extensive consultations in addition to a comprehensive literature review. Best practice
guidelines prepared by national organizations that undergo careful review by representatives
are of the most credible and influential as they are endorsed by respected national bodies and
are subject to intense scrutiny by health care professionals (Fletcher, 2007). The CSS
recommendations include everything from blood pressure management to brain imaging and
treatment to patient rehabilitation (CSS, 2006). The CSS established the National Stroke
Nursing Council in 2005 to promote leadership, communication, advocacy, education, and
research into the area of stroke. The CSS states that there are frequent reports that new
research in stroke does not always reach primary care providers and patients.
The goal of the British Columbia Provincial Stroke Strategy (BCPSS) is to "reduce
the social and economic burden of stroke in BC through optimal prevention and care,
excellence in rehabilitation, and facilitation of successful community re-integration"
(HSFBC&Y, 2005 , p. 15). The BCPSS is based on four principles: comprehensive,
coordinated, evidence-based, and province-wide care. The principles, when implemented,
will improve the continuum of care, in that all health care providers throughout the province
would follow the same standardized guidelines, which are based on evidence. The
recommendation of the BCPSS is to adopt the national guidelines as outlined in the

18
Canadian Stroke Strategy Best Practice Recommendations: 2006. The Canadian Stroke
Strategy (CSS) will provide "the impetus for all provinces and territories to achieve a
coordinated and integrated approach to stroke prevention, treatment and rehabilitation by
2010" (HSFBC&Y, 2005, p.8).
Barriers and Facilitators
In implementing or planning for change, barriers must be identified in order to choose
the most appropriate intervention technique. Although the identification of barriers and
facilitators to the implementation of clinical practice guidelines for stroke care goes beyond
the purpose of this project, a few observations are made here. Lindsay et al. (2008) report
that 77% of hospitals do not have a formal protocol for managing stroke and that the major
factor accounting for varying stroke care is due to the lack of implementation of guidelines.
Rita Sweeney RN, Clinical Lead in Acute MI and Stroke Project, who is identifying and
implementing evidence-based practice recommendations for NHA based on the Provincial
Stroke Strategy (Personal Communication, July, 2008) contends that there are similar
barriers in Northern Health.
Guideline implementation may also be hindered by individual barriers. A clinical
practice guideline may be perceived as inconvenient or difficult to use. A guideline that
recommends the elimination of an established clinical practice of administering
anticoagulartts for stroke and implementing a new behaviour such as administering aspirin
may be difficult for practitioners to accept (Buchan, 2006). The individual health care
provider may not agree with a specific guideline or even the concepts of guidelines in
general. Health care providers may also lack the motivation to change or may not feel
competent to change. McKenna & Keeny (2004) found several specific barriers for

19
physicians to implement evidence-based guidelines: limited relevance of research to practice,
difficulty keeping up with all of the current changes in primary care, and the ability to search
for evidence-based information. The ability to search for evidence-based information is also
noted by Gronseth (2004) as a barrier "results are mixed on whether educating physicians
about evidence-based recommendations is sufficient to change physician behaviour" (p.
335). Gronseth attributes the barriers as physician skepticism, patient expectations, fear of
legal action, and distorted reimbursement systems. Similarly, Miles, Loughlin & Polychroius
(2007) found that although physicians have a positive view of the evidence-based
recommendations and easy access to them, the majority seldom use the internet to search for
information due to time constraints. The Centre for Health Evidence (CHE) (2007) states that
using the findings from systematic reviews constitutes evidence-based medicine and thereby
"de-emphasizes intuition, unsystematic clinical experience, and pathophysiological rationale
as sufficient grounds for clinical decision making, and stresses the examination of evidence
from clinical research". However, CHE also appreciates the new skills required by physician
which includes efficient literature searching as well as the application of formal rules in
evaluating the clinical literature. It is likely that inconsistent care of patients with AIS is
related to the lack of clinical practice guidelines for AIS , differing opinions and
interpretations of evidence by physicians, and differing physicians' training and experience
(Grimshaw et al., 2001).
Although inconsistent practices in the treatment of AIS are experienced in Northern
Health facilities, there are current actions underway that have the potential to remedy this
concern. The work of the Acute MI and Stroke Project which includes assessment of
facilities and staff, education, and guideline implementation, is an important initiative for the

20
health of the people who reside in the Northern Health Authority (Grimshaw et al. (2001).
supports this approach, in stating that the 'effects of implementing guidelines across a range
of settings generally observe improvement in the process of care" (p. 41 ).
Implementing Evidence-based Practice
Evidence-based practice (EBP) "is the conscientious use of current best evidence in
making decisions about patient care" (Sackett, Straus, Richardson, Rosenberg, & Haynes,
2000 in Melnyk & Fineout-Overholt, 2005, p.6). It is crucial that all health care providers
working in primary care base their practice on the most current evidence. Family Nurse
Practitioners have been introduced as primary health care providers in British Columbia, and
are accountable for providing quality patient care. As Family Nurse Practitioners are
prescribing medication, caring for people with chronic diseases, and most importantly,
helping to prevent disease and injury and to promote health, they must be current in their
knowledge because so much of the FNP's role is teaching patients and their families about
their disease and their medication. FNPs, who are increasingly important members of
primary healthcare teams have a responsibility to communicate guidelines effectively to
colleagues through continuing education activities within the team. Through such venues as
weekly rounds, newsletters, email, or journal clubs, FNPs may effect change to health care
providers and health care recipients.
Recommendations
After a thorough review of the current available literature on the treatment of AIS,
it is recommended that the CSS Canadian Best Practice Recommendations for Stroke Care
be incorporated into the treatment of patients with AIS across Northern Health in particular
with relation to the use of antiplatelet therapy and the avoidance of anticoagulant therapy.

21
The CSS recommendations are evidence-based and meet the criteria for credible guidelines
as defined by Fletcher (2007). Further investigation in identifying and choosing appropriate
interventions that will overcome the barriers to implementing new evidence-based clinical
practice guidelines would merit investigation.
Conclusion.
Acute ishaemic stroke is a significant health concern for both health care practitioners
and patients in Northern Health Authority. While there is an identified gap between current
theory and practice of the administration of anti platelet versus anticoagulant therapy,
substantial evidence-based research has demonstrated best treatment for patients with AIS.
The research evidence recommends the administration of aspirin 160 mg- 325 mg over
other antiplatelet agents, and recommends against anticoagulant therapy for the treatment of
AIS. Implementing aspirin therapy in the prevention and treatment of AIS has considerable
economic clinical and economic benefits in Northern Health. Additionally, it is essential for
primary health care providers to develop or follow clinical practice guidelines based on
research to support the best possible patient care. FNPs can play a significant role in this
regard in the primary care team. FNPs emphasize health promotion and disease prevention in
primary, secondary, and tertiary care.

22
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Appendix A (reprinted from R. Fletcher, (2007). Clinical practice guidelines. UpToDate)

Hallmarks of a credible guideline
Expertise
Evidence-based

Broad-based
Recency
Imprimatur
Implementation
Review

!Should include all relevant expertise bearing on the clinical decision
Should have explict, scientifically credible, plans for finding all relevant
research results, weighing the strength of the evidence, and providing
rationale for decisions
Should go beyond effectiveness to look at harm, cost, and other clinicallyrelevant factors
trhe guideline should not be out of date, relative to developments in its
Wield
!Guidelines by respected national organizations are more likely to be
~redible
~uidelines should pay attention to how the recommendations can be
ccomplished in practice, including the workforce and expertise necessary
o do so
uidelines should be shaped not just by the particular panel that drafted
hem, but also by other members of the sponsoring society and other
rganizations

!

~

©2007 UpToDate® • customerservice@uptodate.com

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Appendix B (Reprinted from R. Fletcher. (2007) Evidenced-based medicine. UpToDate

. pract"1ce gu1·de rmes
c·
r1ter1a f or repor t"mg c rm1ca
Objective

f. succinct statement of the objective of the guideline, including the targeted health problem,
he targeted patients and providers, and the main reason for developing recommendations
concerninq this problem for this population.

Options

Principle practice options that were considered in formulating the guidelines.

Outcomes

Significant health and economic outcomes identified as potential consequences of the
practice options.

Evidence

Methods used to gather, select, and synthesize evidence, and the date of the most recent
evidence obtained.

Values

Persons and methods used to assign values (relative importance) to potential outcomes of
alternative practice options.

Benefits, Harms and Costs

The type and magnitude of the main benefits, harms, and costs that are expected to result
from guideline implementation.

Recommendations

,A.brief and sp_ecific list of key recommendations.

Validation

r-he results of any external review, comparison with guidelines developed by other groups,
or clinical testinq of quideline use .

Sponsors

Key persons or groups that developed, funded, or endorsed the guideline.

Adapted from Haywood, SA, Wilson, MC, Tunis, SR, eta/, Ann Intern Med 1993;
118:731.