(Stroke. 1999;30:1218-1222.)
© 1999 American Heart Association, Inc.
Original Contributions |
Risk Assessment and Anticoagulation for Primary Stroke Prevention in Atrial Fibrillation
From the Orpington Stroke Unit, Clinical and Health Services Studies Unit, King's College School of Medicine & Dentistry, London, UK.
Correspondence to Dr L. Kalra, Department of Medicine, King's College School of Medicine & Dentistry, Bessemer Road, London SE5 9PJ, UK. E-mail lalit.kalra{at}kcl.ac.uk
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Abstract |
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Background and Purpose—Risk assessment before anticoagulation is important for effective stroke prevention in atrial fibrillation (AF).
Methods—A study was undertaken in patients with AF to investigate the contribution of clinical and echocardiography (ECHO) criteria to treatment decisions on anticoagulation. Patients were stratified by age and stroke risk; contraindications to anticoagulation and warfarin use were assessed. The value of ECHO in treatment decisions, effect of age, and existing anticoagulation practice were evaluated.
Results—The mean±SD age of 234 patients was 67.1±11.8 years,
and 122 (52%) were women. Clinical risk factors were present in 74
of 80 patients (92%) aged >75 years compared with 99 of 154 patients
(64%) 
75 years (P<0.01). ECHO risk was identified in
94 of 154 patients (61%) 75 years, 16 (17%) of whom had no clinical
risk factors. ECHO risk was present in 71 patients (88%) >75
years of age, and was associated with clinical risk factors in all
patients. Eligibility for anticoagulation was seen in 72 of 154 (47%)
to 105 of 154 (68%) patients aged 75 years, depending on the
criteria used, and in 66 of 80 patients (83%) >75 years, regardless
of criteria used (P<0.01). Warfarin was being used in
55 of 105 patients (51%) 75 years and 8 of 66 patients (12%) >75
years (P<0.001). Anticoagulation was being undertaken
in 7 of 49 patients (14%) 75 years despite no clinical or ECHO
risks.
Conclusions—Accurate assessments of eligibility and
appropriateness of anticoagulation in AF can be made on clinical
criteria alone, especially in older people. The value of ECHO in
treatment decisions is limited to patients 75 years of age with no
clinical risk factors.
Key Words: aged • anticoagulants • atrial fibrillation • echocardiography • prevention, primary • risk factors
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Atrial fibrillation is a known risk factor for stroke, and its incidence increases with age: approximately 6% to 10% of people aged >75 years have AF.1 2 Several randomized controlled studies have shown that adjusted-dose warfarin reduces the overall risk of stroke by 68%: from 5% to 1.3% per year in these patients, with a 1% increase in the risk of major bleeds.1 3 4 5 However, reanalysis of pooled data suggests that the margin between expected benefit and harm may be thinner than believed originally: the reduction in annual incidence of major stroke was <1% and the increase in major bleeding nearly 2%.6 The fears of inappropriate anticoagulation for primary prevention are compounded by research showing a trend toward increasing use of warfarin7 and differences in the case mix, quality of anticoagulation control, and frequency of bleeding complications between randomized trials and clinical practice, which may adversely affect effectiveness.8 Although the most appropriate approach is one that balances the hazards of warfarin use with the expected reduction in stroke risk,9 there are significant differences of opinion on who should be anticoagulated.10 Several earlier studies11 12 13 14 have shown that anticoagulation is underused patients with AF in clinical practice, but the criteria for eligibility vary between studies, and there is little information on inappropriate anticoagulation in patients at low risk of stroke. Because the decrease in risk is proportional to the individual patient's risk of stroke, there is a possibility that anticoagulation without careful risk assessment may reduce the effectiveness of anticoagulation in patients with AF.8
Risk assessment and determination of eligibility for anticoagulation
has been facilitated by the identification of factors that increase
stroke risk in patients with AF.1 3 15 16 17 18 The risk of
stroke in patients with AF aged 75 years is low (1% per year)
in the absence of other vascular risk factors.1 3 15 The
risk is considerably increased (8% to 12%) in patients who are >75
years of age or have other vascular risk factors, such as recent
transient ischemic attack or stroke, hypertension, and diabetes
mellitus.1 3 15 There are several
recommendations1 15 16 17 in the literature on eligibility
for anticoagulation in AF that are based these
criteria,3 5 18 but clinical practice has been made
difficult by the wide range of guidelines available currently and the
variations in their content.10 It may be possible to
refine patient selection for anticoagulation by using
echocardiography in the determination of
risk.19 However, the routine availability of
echocardiography for such assessments may be
limited, not only in the developing world but also in developed
countries such as Great Britain.20 In addition, the
contribution of echocardiography over and above
that of clinical criteria in the selection of patients for
anticoagulation is unclear because there is little information on how
frequently echocardiography is the only method that
will identify stroke risk in patients with AF.
The objective of this study was to evaluate the role of clinical and echocardiographic criteria in determining eligibility for anticoagulation for primary prevention of stroke. The appropriateness of existing clinical practice and the effects of age on anticoagulation decisions were also evaluated.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The study was undertaken in a suburban district general hospital serving a population of 310 000. Stroke prevention was a major strategic priority within the national health program21 and was supported by several local initiatives in primary care, stroke clinics, and free anticoagulation services.
Subjects were recruited from a random sample of unselected patients attending general medical outpatient clinics over a 12-month period. All patients aged <90 years with a diagnosis of AF on routine ECG examination of at least 2 months' duration were considered eligible for inclusion. Patients receiving anticoagulation for other indications (such as pulmonary emboli or deep-vein thrombosis) were excluded from the study.
All patients underwent a detailed clinical examination, which included assessments for the cause and duration of AF, and other evidence of cardiovascular disease and heart failure. An ECG was undertaken to confirm the diagnosis of AF. Patients were screened for vascular risk factors using a recommended protocol22 and for risk of bleeding complications and comorbidity or medication that might influence anticoagulant use. Investigations included full blood counts, coagulation profile, and renal and hepatic function tests. Transthoracic echocardiography was undertaken by a trained technician for left atrial size, left ventricular dysfunction, cardiomyopathy, and valvular disease, using M-mode and 2-dimensional imaging. In addition, a range of sources including patients, medical records, and general practice notes were used to collect data on treatment decisions with warfarin in these patients.
Stroke risk was assessed on clinical and echocardiographic criteria. The clinical criteria were derived from pooled data of clinical trials, including Stroke Prevention in Atrial Fibrillation (SPAF) studies and recommendations from existing guidelines.3 15 16 17 18 Criteria for high risk of stroke (>8% per year) included a history of transient ischemic attack or recent stroke, previous thromboembolism, hypertension (particularly systolic hypertension), diabetes, congestive heart failure, and age >75 years. The high-risk group also included patients with valvular disease, cardiac prosthesis, or recent heart failure. Echocardiographic criteria for high risk of stroke were based on the SPAF studies and included left atrial enlargement of >2.5cm/m2, left ventricular dyskinesia, cardiomyopathy, or intracardiac thrombus.19
In the absence of accepted guidelines, the contraindications for anticoagulation were based on known contraindications to anticoagulation and exclusion criteria used in clinical trials.3 5 18 Major contraindications to warfarin use included a history of bleeding from the gastrointestinal or genitourinary tract in the 6 months prior to diagnosis, known coagulation defects, thrombocytopenia or platelet dysfunction, hemorrhagic stroke, excessive alcoholic intake, recurrent falls, and poor drug or clinic compliance. Minor contraindications included uncontrolled hypertension and the use of nonsteroidal agents.
The approach used was to balance the hazards of warfarin with the likely absolute decreases in stroke risk. Because this reduction is proportional to patients' absolute risk of stroke, patients at high clinical or echocardiographic risk identified by above criteria will benefit most and need to be anticoagulated in the absence of contraindications to warfarin use. The value of echocardiography was assessed by recording the frequency at which this was the only method of identifying the need for anticoagulation.
Descriptive data are presented as mean, median, or proportion,
as appropriate. Analysis was performed with the
2 test for comparisons of independent
proportions in >2 groups, except for data that include 0 as a value.
This test has been chosen because of its simplicity and robustness for
such analyses. The bivariate association between use of
warfarin and age, gender, level of stroke risk, individual vascular
risk factors, and contraindications to anticoagulation also was
assessed with the 2 test.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Of the 2457 patients seen in medical clinics over the study period, AF demonstrated on ECG was present in 344 patients (14%). The median duration between the first diagnosis of AF and research assessment was 17.5 months (range, 2 to 34 months). Echocardiography was undertaken in 234 patients (68%), 154 (66%) of whom were
75 years and 80 (33%) of whom were
>75 years of age. The proportion of patients aged >75 years who had
an echocardiogram [80/110 (72%)] was comparable with patients aged
75 years [154/234 (66%)].
The mean±SD age of the 234 patients included in the study was
67.1±11.8 years (range, 47 to 88 years), and 122 (52%) were women.
There were significantly more women in the older than in the younger
age group (45/80 versus 68/154; P<0.05). Vascular risk
factors other than AF or age were significantly more common in the
older age group and were present in 74 of 80 patients (92%) aged
>75 years compared with 99 of 154 patients (64%) aged 75 years
(Table 1
).
Echocardiographic risk was identified in 94 of 154
patients (61%) 75 years of age, 16 (17%) of whom had no clinical
risk factors (Table 1). Echocardiographic risk
was significantly more prevalent in patients >75 years of age (88%)
and was associated with clinical risk factors in all patients
(Table 1).
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A contraindication to anticoagulation was present in nearly 40% of
patients aged >75 years, nearly half of whom (18%) had a major
contraindication and were ineligible for anticoagulation (Table 2). The proportion of patients aged 75
years who had contraindications to anticoagulation was significantly
lower (18% versus 37%, P<0.05) compared with the older
age group. Major contraindications were significantly less common in
patients 75 years of age (6% versus 18%; P<0.05), but
there were no significant differences between the frequency of minor
contraindications between the 2 age groups (Table 2).
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There was a significant difference in the proportion of patients aged
75 years who were eligible for anticoagulation, depending on criteria
used. This proportion increased from 58% to 68% when
echocardiographic criteria were used in addition to
clinical criteria, but it fell to 47% when both clinical and
echocardiographic criteria had to be satisfied before
anticoagulation (Table 3). In contrast,
there were no significant differences in the proportion of patients
>75 years of age who were eligible for anticoagulation, regardless of
whether clinical criteria were used alone or in combination with
echocardiographic criteria.
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The study shows a significant age effect in the eligibility for
anticoagulation. Nearly all patients aged >75 years with no
contraindications to warfarin were eligible for anticoagulation because
of the high prevalence of risk factors in this age group (Table 3
). However, only 12% patients of these patients were being
anticoagulated compared with >50% of patients 75 years of age who
were receiving warfarin. Risk assessment showed that treatment with
warfarin would not be indicated in at least 32% patients 75 years
because of low risk or major contraindications to anticoagulation,
regardless of the criteria used. Despite this, a significant number of
patients were being anticoagulated, and their proportion varied between
14% and 26%, depending on the criteria used (Table 3).
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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One of the most important recent advances in primary stroke prevention is the demonstration that warfarin can substantially reduce the risk of stroke in patients with AF.1 However, not all patients with AF will benefit equally by long-term anticoagulation, and the greatest benefit will be seen in those with the greatest risk of stroke. Although there are several published reports and recommendations that provide criteria to identify high-risk patients,1 3 15 16 17 reliable identification of eligible patients remains difficult because of the wide range of advice available and the lack of consensus between different recommendations.10 This difficulty has been reflected in the present study, which shows that the proportion of patients who can be considered eligible for anticoagulation (and have no major contraindications) varied from 47% to 68% in those aged
75
years, depending on the combination of clinical and
echocardiographic criteria used. These results are in
agreement with a recently published study2 which showed
that about one half to two thirds of patients with AF need
anticoagulation for primary prevention depending on the criteria
used. The problems of assessing stroke risk are compounded by the absence of clear guidelines on contraindications to anticoagulation. The contraindications used in this study are based on accepted practice and exclusion criteria used in major studies on anticoagulation in AF. The results suggest that although contraindications to anticoagulation may be present in about 40% of patients, especially in the older age groups, the majority of these are minor and can be reversed by aggressive treatment of hypertension, altering medication or encouraging compliance in most patients. This has the potential of greatly increasing the numbers of patients who can be safely treated, thus improving the effectiveness of anticoagulation for stroke prevention in AF.
The role of echocardiography in risk assessment is
of interest. The need for echocardiography depends
on the selection criteria used and its usefulness in influencing
anticoagulation decisions in clinical practice. This study suggests
that the role of this investigation in determining stroke risk may be
less important than assumed previously, especially in patients >75
years of age. Results show that echocardiographic risk
is seldom present in older patients without clinical risk factors
also being present, even when age is not taken into account (Table 2). Treatment decisions in this age group can be made on
clinical grounds alone, without resorting to
echocardiography. On the other hand,
echocardiography is important in determining risk
in patients 75 years of age. The study showed that a significant
proportion of these patients had echocardiographic risk
in the absence of clinical risk factors (Table 2) and would not
have been identified if clinical criteria alone were used. The study
suggests that treatment decisions to anticoagulate can be made safely,
without recourse to echocardiography, in all
patients who have clinical risk factors and no contraindications to
anticoagulation, regardless of the age of patient.
Echocardiography is needed to determine eligibility
for anticoagulation in a small proportion of patients 75 years of age
who have no clinical risk factors or contraindications to
anticoagulation.
The other problem identified in the study was that a large proportion
of patients at high risk of stroke do not receive appropriate
treatment, especially in the older age group. Atrial fibrillation is 5
to 10 times more common in patients aged >75 years who are also at a
higher risk of stroke.1 The higher prevalence of stroke
risk on clinical and echocardiographic criteria with
patients aged 75 years was confirmed in this study (Table 1).
The proportion of older patients who will benefit by anticoagulation
also was significantly greater than that of younger patients, even when
contraindications to anticoagulation were taken into account (Table 3). Despite this, the use of anticoagulation was significantly
influenced by age, with very few people >75 years of age being
anticoagulated. These findings contrast with surveys that show a high
level of physician agreement on the effectiveness of anticoagulation
and warfarin use, even in elderly people.23 However, they
are in keeping with observed practice of reluctance to use warfarin in
older patients, either because of lack of knowledge of the relative
impact of individual risk factors or poor evaluation of risk in this
age group.24 The message from this and other studies is
that age alone should not be one of the major determinants for
appropriateness of anticoagulation in patients with
AF.1 2 24 Clinical emphasis should be on identifying older
patients who have no contraindications to anticoagulation because they
are most likely to receive the greatest benefit from regular warfarin
use.
Overall, there is little doubt that anticoagulation is being underused
in patients with AF at high stroke risk, regardless of age or criteria
used.2 11 12 13 14 This study also showed that 15% to 25%
patients aged 75 years who did not meet clinical and/or
echocardiographic criteria for eligibility were being
anticoagulated. A previous study has shown that there is an increasing
trend toward the use of warfarin in AF,7 and it is clear
that some of the current anticoagulation practice needs to be
redirected. The lack of consensus on eligibility makes it difficult to
assess the true extent of underutilization of anticoagulation in
high-risk patients or inappropriate use of warfarin in patients at low
risk of stroke. In addition, because effectiveness of anticoagulation
is dependent on maintaining INR in the target range and preventing
complications,8 facilities are required for regular
follow-up of patients, many of whom will be elderly. These issues are
important in clinical practice for estimating the extent of need and
the level or type of services required to initiate and monitor
anticoagulation.25 This study highlights the need for
clear and simple guidelines for risk assessment that are age sensitive
and allow unequivocal treatment decisions to be taken, using a
standardized risk-assessment algorithm. There is little doubt that such
consensus will improve the efficacy and effectiveness of
anticoagulation and allow precise quantification of service resource
needs.26
Received February 23, 1999; revision received March 15, 1999; accepted March 16, 1999.
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