Af economic analysis

Costs and Benefits of Antithrombotic
Therapy in Atrial Fibrillation in England:
An Economic Analysis based on GRASP-AF
Marion Kerr
Insight Health Economics for NHS Improving Quality
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Acknowledgements
2
We would like to acknowledge PRIMIS who helped
develop the GRASP-AF tool in partnership with NHS
IQ and who freely provided the software tools to run
GRASP-AF and upload data. We would also like to
acknowledge the practices that have voluntarily
uploadeddatatotheCHARTOnlinedatabase,without
whom this report would not have been possible.
“
“

Executive Summary
1. We estimate that more than 900,000 people in England (1.74% of the population) have atrial
fibrillation (AF). AF is associated with increased risk of stroke and heart failure, and with premature
mortality, independent of other known risk factors.
2. We use an extract from the GRASP-AF dataset, covering 13% of the population of England, to estimate
England-level prevalence and prescribing patterns. Based on GRASP-AF and evidence from clinical studies,
we develop a Markov model to estimate the long-term impact of antithrombotic prescribing in AF on
stroke and major bleed incidence, mortality, quality-adjusted life years (QALYs), and National Health
Service (NHS) and social care costs.
3. We estimate that around 16,100 strokes a year, including 4,400 fatal strokes, are averted in people
with AF who are taking warfarin (or warfarin plus aspirin). Fatal strokes are defined as those in which the
patient dies within 30 days. However, disabling strokes also increase the risk of death over the longer
term. Owing to the reduction in disabling strokes associated with warfarin, further deaths are averted.
Total deaths in people with AF who are taking warfarin (or warfarin plus aspirin) are reduced by an
estimated 4,800 over a one-year perspective. However, while these medications reduce stroke risk and
mortality, they do increase the risk of bleeding. We estimate that there are 2,800 excess major bleeds a
year in people with AF who are taking warfarin or warfarin plus aspirin.
4. Recent National Institute for Health and Care Excellence (NICE) guidelines recommend that the
CHA2DS2-VASc algorithm should be used to assess stroke risk in people with AF, and that anticoagulants
should be offered to those with a CHA2DS2-VASc score of 2 or more, taking bleeding risk into account.
However, in our dataset only around half of those who meet the prescribing criteria (53.60%) are taking
anticoagulants. For 8.74%, it is recorded that anticoagulants are contraindicated or declined. It is likely
therefore that there are substantial numbers of people with AF who would benefit from anticoagulation
therapy but are not receiving it.
5. Our model suggests that if warfarin were prescribed for all those in England with a CHA2DS2-VASc
score of 2 or more (apart from those for whom the record states that anticoagulants are contraindicated
or declined) a further 11,600 AF-related strokes, including 3,200 fatal strokes, would be averted each
year. There would be an additional 1,500 excess bleeds, and the total number of deaths in people with
AF, over a one-year perspective, would be reduced by 3,500.
6. Our analysis suggests that warfarin prescribing for people with AF is associated with an overall
reduction in the NHS cost of AF-related care, as savings from averted strokes exceed the combined cost of
treatment and associated major bleeds. We estimate that, over a lifetime, 0.30 strokes are averted, 0.79
QALYs are gained and net savings of more that £2,400 are generated for the NHS per person with AF
treated with warfarin. We estimate that if everyone in England with a CHA2DS2-VASc score of 2 or more
(apart from those for whom the record states that anticoagulants are contraindicated or declined) received
warfarin, the NHS would save approximately £124 million a year, relative to current patterns of care. There
are further estimated savings to social care.
7. While the focus in this paper is on NHS and social care costs, strokes associated with AF will also entail
costs for individuals and their carers, and for society through losses in employment and productivity, and
tax and benefit effects. If these effects were considered, it is likely that the overall savings from averted
strokes would be higher than those estimated here.
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ExecutiveSummary
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Introduction
1. The prevalence of atrial fibrillation (AF) has been estimated at 1-2% of the population in the developed
world.1,2,3,4
AF is associated with increased risk of stroke and heart failure, and with premature mortality,
independent of other known risk factors.5,6
2. Current management of AF is focused on rate/rhythm control and reduction of stroke risk, primarily
through anticoagulation therapy. In the English NHS the Quality and Outcomes Framework (QOF) has,
since 2006-07, provided financial incentives to general practitioners for the formation of AF registers, and
for treatment of the condition with anticoagulation or antiplatelet therapy. The QOF data for 2012-13
indicate that 849,407 people in England had diagnosed AF, a population prevalence of 1.5%.
3. The National Institute for Health and Care Excellence (NICE) has recently issued guidelines
recommending that the CHA2DS2-VASc algorithm should be used to assess stroke risk in people with
AF, and that anticoagulants should be offered to those with a CHA2DS2-VASc score of 2 or more, taking
bleeding risk into account.7
Anticoagulation should also be considered for men with a CHA2DS2-VASc
score of 1, again taking bleeding risk into account. The guidelines recommend that aspirin monotherapy
should not be offered solely for stroke prevention to people with atrial fibrillation.
4. The CHA2DS2-VASc algorithm is a point system in which 2 points are assigned for a history of stroke or
transient ischaemic attack (TIA), or age ≥75; and 1 point each is assigned for age 65–74 years, a history of
hypertension, diabetes, recent cardiac failure, vascular disease and female sex.
5. In this paper we examine antithrombotic prescribing patterns for people with AF in England, based on
data from 1,016 GP practices uploaded to the Guidance on Risk Assessment and Stroke Prevention for
Atrial Fibrillation (GRASP-AF) dataset in 2011 and 2012. We estimate the impact of warfarin, and warfarin
plus aspirin prescribing on stroke incidence and on NHS and social care costs, and the potential impact of
prescribing warfarin to all those with a CHA2DS2-VASc score of 2 or more. In a supplementary appendix
we also provide illustrative analysis of the impact on stroke incidence and costs of aspirin monotherapy.
Methods
1. Details of AF status and care were obtained from GRASP-AF for 1,016 GP practices in England.
Together, these practices provide primary care to 7.1 million people, approximately 13% of the
population of England. Data were uploaded to GRASP-AF between November 2011 and July 2012.
2. The GRASP-AF dataset provides pseudonymised patient-level data on AF status, age, gender,
CHA2DS2-VASc score, prior stroke status and antithrombotic prescribing for GP practices that choose to
participate.
3. The age distribution of patients in practices included in the data extract was compared with that
reported for the population of England in Office for National Statistics (ONS) mid-year data for 2012.8
AF prevalence estimates from the GRASP-AF dataset were applied to the ONS population of England by
5-year age-band. The resulting AF prevalence estimates for England were compared with the prevalence
recorded in QOF for 2012-13.
4. The distribution of patients with AF in England in 2012-13 by CHA2DS2-VASc score and prior stroke
status was estimated by applying the GRASP-AF proportions to the 2012-13 AF prevalence estimates for
England. The volumes of anticoagulant and antiplatelet prescribing were estimated by applying the
GRASP-AF proportions by CHA2DS2-VASc score and prior stroke status.
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5. A Markov model was built to estimate the impact of warfarin monotherapy, and warfarin plus aspirin
combination therapy on stroke incidence, mortality, QALYs and NHS and social care costs. The model was
also used to estimate the impacts of aspirin monotherapy. However, there is uncertainty regarding the
efficacy of aspirin in reducing stroke risk in AF. In a recent meta-analysis, the estimate for the impact of
aspirin did not reach statistical significance at the 95% level.9
For this reason, the results of the aspirin
monotherapy analysis are provided in a supplementary appendix to this paper. Care should be taken in
interpreting the aspirin results owing to the uncertainty surrounding the meta-analysis estimate.
6. Markov models are commonly used in health economic evaluations, in particular where it is necessary
to extrapolate beyond study results, and where diseases present with recurrent events.10
A Markov model
consists of a finite set of health states in which an individual can be found. The model runs over a series
of cycles, and patients move between states or stay in the same state over time, with movements defined
by transition probabilities. Costs and QALYs are assigned to each health state and earned at the end of
each cycle. In this case the Markov states are AF without stroke, AF plus acute ischaemic or haemorrhagic
stroke (each sub-divided into disabling, moderate and mild stroke), AF plus prior stroke (again sub-divided
into disabling, moderate and mild), major non-intracerebral intracranial bleed with or without prior stroke,
major extracranial bleed with or without prior stroke, and dead. The AF plus acute stroke states and bleed
states are transitional; individuals can stay in them for only one cycle (though return to these states is
possible if repeated strokes or bleeds are experienced). The cycle length is three months. The structure of
the Markov model, indicating the states and possible transitions, is shown in Figure 1.
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Figure 1: Markov model structure
Death
AF plus
prior stroke
Major bleed
in AF plus
prior stroke
Major bleed
in AF without
stroke
AF plus
acute ischaemic/
haemorrhagic stroke
Mild Moderate
Disabling
Mild Moderate
Disabling
AF
without
stroke

7. In cost effectiveness analysis it is customary to express costs and effects over the lifetime of a
representative patient. Indeed, for the estimation of QALY effects it is necessary to take such a long-term
perspective. However, decision-makers often wish also to understand costs over shorter timescales. In this
paper we therefore present long-run (“lifetime”) cost and QALY impacts, and also one-year cost impacts.
The representative patient is taken to be 78 years old at model outset, based on the median age in
GRASP-AF.
8. The baseline risk of ischaemic stroke without antithrombotic treatment was estimated by
CHA2DS2-VASc score for the GRASP-AF population, using risks estimated in a recent Swedish study.11
9. There are a number of challenges in estimating the baseline risk of major bleeds, and the effect
of treatment on this risk. Published estimates of major bleed rates in patients taking oral vitamin K
antagonists such as warfarin range from 1.3 to 7.2% a year.12
These differences may reflect variation in a
number of factors, including study populations, stability of international normalised ratio (INR) values,
methodology, definition and classification. Relatively few studies have examined bleed rates in patients
who are not receiving antithrombotics. Some studies have included intracerebral haemorrhage with
stroke, rather than with bleeds, some have included all intracranial bleeds with stroke, while others have
classified all intracranial bleeds as major bleeds rather than strokes. In their 2007 meta-analysis, Hart et al.
did not estimate the impact of warfarin or aspirin versus placebo or control on the relative or absolute risk
of intracranial bleeds, owing to the large proportion of empty cells in individual trial data.9
10. However, in spite of these difficulties we felt it was important to try to model intracerebral
haemorrhages (taken to be equivalent to haemorrhagic strokes) discretely; while such haemorrhages are
far less frequent than ischaemic strokes, mortality rates are very high (more than 50% in many
studies).13,14
We estimated the rate of all intracranial bleeds in patients with AF on warfarin at 0.73% per
year, based on a weighted average from 16 randomised trials summarized by Lip et al.12
Most of these
studies did not distinguish between intracerebral and other intracranial bleeds. The RE-LY trial (which was
included in the 16) reported that 46% of intracranial bleeds were intracerebral. (The rate of intracranial
bleeds in this trial was 0.76%).14
Applying this proportion to the overall estimate derived from the 16
trials, we estimate the rate of intracerebral haemorrhage in warfarin at 0.34%, and the rate of other
intracranial haemorrhage at 0.39%.
11. Of the 16 studies summarized by Lip at al., one provided an estimate of the rate of intracranial bleed
in the absence of warfarin.15
This study estimated a crude rate ratio of 1.96 (95% CI 1.25-3.03) for
intracranial bleed in those taking warfarin, relative to the non-warfarin group. It should be noted that
some of the non-warfarin group were taking aspirin. The study did not provide discrete data for the
aspirin and non-antithrombotic sub-groups. A US study of 13,559 people with AF reported that the risk of
intracerebral haemorrhage was 1.81 times higher in patients on warfarin than in those who were not on
warfarin.16
Applying these proportions to the estimates of bleed rates in warfarin set out in paragraph 10,
we estimate the baseline risk of all intracranial bleeds without warfarin at 0.37%, and the baseline risk of
intracerebral bleed at 0.19%.
12. No studies were identified which provided discrete intracerebral haemorrhage risk estimates by
CHA2DS2-VASc score or prior stroke status, though some studies have suggested that the absolute
increase in risk for intracranial haemorrhage due to warfarin therapy remains fairly stable across
thromboembolic risk categories.16
GRASP-AF does not classify patients using HAS-BLED or other
bleed risk measures.
13. Hart et al. estimated in their meta-analysis that warfarin was associated with an absolute increase in
the risk of major extracranial bleeds of 0.3% per year, relative to control or placebo, and this figure was
used in the model.9
14. The impact of warfarin on the combined endpoint of stroke and intracranial bleed risk was estimated
by Hart et al. in their 2007 meta-analysis findings at minus 64%.9
Adjusting that figure for the increase in
risk of intracranial bleeds, we estimate the reduction in ischaemic stroke risk to be 66.88% for patients
with prior stroke and 69.70% for those without prior stroke.
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15. We have assumed that ischaemic stroke reduction in the case of treatment with both warfarin and
antiplatelets is the same as for warfarin alone. The hazard ratio for major bleeds in combined therapy
relative to warfarin monotherapy is taken to be 1.53.18
It should be noted that this approach may
underestimate the risk of intracranial haemorrhage when both warfarin and aspirin are taken. Some
studies have suggested that the relative risk of intracranial haemorrhage in warfarin and aspirin
combination therapy, relative to warfarin monotherapy, may be up to 2.4.19
16. We followed the practice of Ali et al. in defining minor bleeds as those that do not require medical
intervention.20
We did not model any cost or outcome impacts for these events.
17. Thirty-day ischaemic stroke mortality rates in AF for those without antithrombotic therapy, for patients
on warfarin, and for those on aspirin were estimated from a US study.21
Thirty-day mortality rates after
haemorrhagic stroke and other intracranial bleeds were taken from the RE-LY trial.14
Hazard ratios for
subsequent death after non-fatal ischaemic stroke, haemorrhagic stroke and other major bleeds were
taken from the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events
(ACTIVE)-W Trial.22
Mortality risk in AF in the absence of stroke or major bleed, was estimated from ONS
Life Tables by gender and year of age. The overall mortality rates predicted in the model for people on
warfarin were validated by comparing with meta-analysis findings on the absolute reduction in all-death
risk.9
18. The NHS costs of the first 90 days of care for mild, moderate, disabling and fatal strokes were
estimated from a recent UK study on stroke in AF.23
The impact of stroke in AF on social care costs for
mild, moderate, and disabling strokes was estimated from the same report. The study also provided
estimates of the difference between ongoing post-stroke (after 90 days) and pre-stroke NHS costs.
However, these estimates were not statistically significant at the 95% level. We therefore excluded them
from our base-case analysis, but have included them in sensitivity analysis.
19. The proportion of disabling strokes in AF, by treatment modality, was taken from Hart et al.9
Of the
remainder, the distribution of moderate and mild strokes in patients with AF was taken from the US
Framingham study.24
20. The mean costs of major extracranial bleeds and non-intracerebral intracranial bleeds were estimated
from NHS Reference Costs.25
The weighted mean cost of admission episodes grouped to HRGs FZ38G-P,
Gastrointestinal Bleed (£1,092) was used to estimate the cost of extracranial bleeds. The weighted mean
cost of admission episodes grouped to HRGs AA23C-G, Haemorrhagic Cerebrovascular Disorders (£2,589)
was used to estimate the cost of non-intracerebral intracranial bleeds. (While these HRGs are labeled as
cerebrovascular, ICD 10 codes I60 and I62.0, covering subarachnoid and subdural haemorrhages
respectively, are also grouped to these HRGs).
21. The costs of medications were taken from the British National Formulary (BNF).26
The mean daily dose
of warfarin was assumed to be 4mg.27
Warfarin tablets are available in 0.5mg, 1 mg, 3mg, and 5mg
doses. The cost of the medication varies substantially, depending on the combination of tablets used to
administer a given dose, as shown in Table 1.
Table 1: Annual cost of warfarin medication, by dose and tablet combination Source: BNF 6426
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Dose and cost Tablet combination
4mg daily dose 8 x 0.5mg 4 x 1mg 1 x 1mg + 1 x 3mg 2 x 0.5mg + 1 x 3mg
Annual cost £174.16 £44.84 £22.42 £54.75
6mg daily dose 12 x 0.5mg 2 x 3mg 1 x1mg + 1 x 5mg 2 x 0.5mg + 1 x 5mg
Annual cost £261.24 £22.42 £23.20 £55.53

22. It is assumed here that 4mg is provided as 1 x 3mg tablet plus 2 x 0.5mg tablets, to allow for dose
adjustment. We have also set out the cost of a 6mg dose, for a variety of tablet combinations (Table 1). If
6mg is delivered as 1 x 5mg and 2 x 0.5mg tablets, the cost is similar to that for 4mg delivered as 1 x 3mg
tablet plus 2 x 0.5mg tablets (£55.53, as compared with £54.75). We did not therefore explore in the
model separate costs for provision of a 6mg daily dose. The mean daily aspirin dosage was taken to be
75mg, and the annual cost was estimated at £6.19.
23. The annual cost of warfarin management, including anticoagulation testing for dose adjustment, has
been estimated in studies at £73.99-£115.60 (after conversion to 2012-13 prices).20,28
The mean value
(£94.80) was used in our base case analysis. It is reported, however, that there is considerable variation in
the cost of warfarin management. In sensitivity analysis we therefore used a range of values for warfarin
monitoring, as recommended in a recent NICE guideline.29
24. Quality of life in patients with atrial fibrillation and in those who have had strokes was estimated
using the EQ-5D standardised measure of health status. Measures were drawn from studies that used
weights derived from UK population preferences.30,31,32
25. Cost and QALY impacts were estimated for current prescribing patterns for patients with
CHA2DS2-VASc score ≥2, based on GRASP-AF data. Cost and QALY impacts were also modelled for
prescribing of warfarin for all those with CHA2DS2-VASc score ≥2 for whom anticoagulants are not
contra-indicated or declined.
26. All costs are expressed in 2012-13 prices. Where necessary, costs were updated using the Hospital and
Community Health Services Pay and Prices index. Future costs and QALYs are discounted at 3.5% a year.
27. A summary of parameters used in the Markov model is provided in Appendix 1, Tables A1.1 and A1.2.
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8%
7%
6%
5%
4%
3%
2%
1%
0%
0-4
Percentageofpopulation
5-9
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
80-84
85-89
90+
60-64
65-69
70-74
75-79
Age
GRASP-AF
ONS
Results
Prevalence and prescribing
1. The GRASP-AF dataset recorded 128,293 people with AF in participating practices, a prevalence of
1.81%. The age distribution of patients in these practices is broadly similar to that reported for England in
ONS, although a somewhat larger proportion of the GRASP-AF population than the ONS population is
aged 65+ (17.56%, as compared with 16.44% in ONS (Figure 2)).
Figure 2: Age distribution by quinary age-band, GRASP-AF, and ONS 2012
2. The prevalence of AF in GRASP-AF ranges from 0.01% in those aged 0-29 years to 15.06% in those
aged ≥ 80 years.
3. Adjusting for the difference in age distribution, the prevalence of AF in England based on GRASP-AF is
estimated at 1.74% in 2012 (929,856 people), as compared with 1.52 % (849,407 people) recorded in
QOF in 2012-13. QOF data exclude patients who are considered to have “AF resolved”. If this group were
removed from GRASP-AF the estimated age-adjusted prevalence for England would be 1.51%. Patients
with “AF resolved” are included in the analyses reported in this paper.
4. Of AF patients in GRASP-AF, 18.14% had a prior stroke, a further 66.00% had a CHA2DS2-VASc score
≥ 2 without prior stroke, 7.64% were men with CHA2DS2-VASc score = 1, 2.40% were women with
CHA2DS2-VASc score = 1, and 5.81% had CHA2DS2-VASc score = 0.
5. Of those with CHA2DS2-VASc score ≥2, 53.60% were prescribed anticoagulants. For 8.74%, the record
stated that anticoagulants were contra-indicated or had been declined (Table 2). Of those in this group
receiving anticoagulants, 99.00% were receiving warfarin.

Table 2: Prescribing of anticoagulants for AF patients in GRASP-AF
6. Anticoagulant and antiplatelet combination therapy was prescribed for 7.78% of those with
CHA2DS2-VASc score ≥ 2, and a further 35.63% were on antiplatelet monotherapy. No antithrombotics
were prescribed for 10.76% of the group (Table 3).
Table 3: Prescribing of anticoagulants and antiplatelets, GRASP-AF
7. If it is assumed that the prevalence of AF and the distribution of CHA2DS2-VASc scores in England is the
same as the age-adjusted estimates from GRASP-AF, it is estimated that there were 783,592 people in
England in 2012-13 with diagnosed AF and a CHA2DS2-VASc score ≥ 2, and 71,519 men with a
CHA2DS2-VASc score = 1.
CHA2DS2-VASc ≥ 2 Men with CHA2DS2-VASc = 1
Patients 107,949 9,810
Anticoagulants Warfarin 53.07% 42.33%
Acenocoumarol 0.32% 0.24%
Dabigatran etexilate 0.12% 0.19%
Phenindione 0.09% 0.06%
Rivaroxaban 0.00% 0.01%
Apixaban 0.00% 0.00%
Anticoagulants contra-indicated 5.44% 2.13%
Anticoagulants declined 3.30% 1.81%
No anticoagulants and anticoagulants not contra-indicated
or declined
37.66% 53.21%
CHA2DS2-VASc ≥ 2 Men with CHA2DS2-VASc = 1
Anticoagulant only 45.82% 36.80%
Anticoagulant and antiplatelet 7.78% 6.04%
Antiplatelet only 35.63% 36.22%
Neither anticoagulant nor antiplatelet 10.76% 20.94%
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Estimated baseline stroke risk
8. Stroke risk in the absence of antithrombotic therapy was estimated by applying stroke risks for each
CHA2DS2-VASc score (2-9) observed in a recent Swedish study11
to the GRASP-AF population, as shown in
Table 4.
Table 4: Stroke risk by CHA2DS2-VASc score (Source: Friberg et al.11
), and distribution of patients in GRASP-AF with and
without prior stroke
9. Given the distribution of patients by CHA2DS2-VASc score in GRASP-AF, we estimate the overall
annual ischaemic stroke risk for the population with CHA2DS2-VASc score ≥ 2 at 4.75% for primary stroke
and 9.38% for secondary stroke, in the absence of antithrombotic therapy. This compares with
meta-analysis findings for the general AF population (not differentiated by CHA2DS2-VASc score) of
4.1% for primary stroke and 13% for secondary stroke, again in the absence of antithrombotic therapy.9
It should be noted, however, that the meta-analysis includes haemorrhagic strokes, whereas the Swedish
study does not.
10. If it is assumed that the prevalence of AF and the distribution of CHA2DS2-VASc scores in England is
the same as the age-adjusted estimates from GRASP-AF, the Markov model estimates that, without any
antithrombotic therapy, there would have been 45,608 strokes (ischaemic and haemorrhagic) in people
with AF with CHA2DS2-VASc score ≥ 2 in England in 2012-13, equivalent to 5.8 for every 100 patients.
Stroke, QALY and cost impacts per person treated, by treatment modality
11. It is customary in health economic analysis to estimate cost and benefit impacts relative to the next
best treatment option. In the case of warfarin in AF, there is uncertainty as to whether the next best
option is no treatment or treatment with aspirin. As indicated above, the meta-analysis estimate of the
impact of aspirin on stroke risk did not reach statistical significance at the 95% level.9
Recent European
Society of Cardiology (ESC) guidelines state that “The evidence for effective stroke prevention with
aspirin in AF is weak, with a potential for harm”.4
As indicated above, NICE has recommended that
aspirin monotherapy should not be offered solely for stroke prevention to people with atrial fibrillation.7
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Distribution of people with AF in GRASP-AF
(% of those with CHA2DS2-VASc score ≥ 2)
CHA2DS2-VASc score Prior stroke No prior stroke Stroke risk (Friberg et al.)
2 374 (0.35%) 20,051 (18.57%) 2.5
3 1,264 (1.17%) 27,191 (25.19%) 3.7
4 3,550 (3.29% 24,765 (22.95%) 5.5
5 6,578 (6.09%) 10,008 (9.27%) 8.4
6 7,357 (6.82%) 2,371 (2.20%) 11.4
7 3,206 (2.97%) 286 (0.26%) 13.1
8 829 (0.77%) 0 (0.00%) 12.6
9 119 (0.11%) 0 (0.00%) 14.4

12. In view of this uncertainty, and the NICE recommendation that aspirin monotherapy should not be
offered for stroke prevention in AF, we have taken no treatment as the next best option in this paper. In
the Appendix we provide illustrative figures for the potential impact of aspirin on stroke. It should be
noted, however, that these estimates are based on the (non-significant) estimates from meta-analysis.
We cannot be confident, at the 95% level, that aspirin reduces the risk of stroke in AF.
13. The Markov model estimates that, over a lifetime perspective, 0.30 strokes (combined ischaemic
and haemorrhagic) are averted and 0.79 QALYs gained per person treated with warfarin, relative to no
antithrombotic treatment. Of averted strokes, more than a quarter (0.08 per person treated) are fatal
strokes. There are 0.05 excess bleeds (extracranial and non-intracerebral intracranial). NHS and social care
costs related to AF are reduced over both a one-year and lifetime perspective, owing to reduced stroke
incidence (Table 5). More details of the NHS cost impact are shown in Table 6.
Table 5: Estimated one-year and lifetime stroke, major bleed, QALY and cost impacts per person treated with warfarin
monotherapy, relative to no antithrombotic therapy
Table 6: Estimated one-year and lifetime NHS cost impacts of treatment, major bleeds and averted strokes per person
treated with warfarin monotherapy, relative to no antithrombotic therapy
14. Fatal strokes are defined as those in which the patient dies within 30 days. However, disabling strokes
also increase the risk of death over the longer term. Owing to the reduction in disabling strokes associated
with warfarin, further deaths are averted. The model estimates that absolute all-cause one-year mortality
is 1.17% lower with warfarin than with no treatment. This estimate may be compared with meta-analysis
findings that warfarin is associated with a 1.6% reduction in all-cause annual mortality.9
15. For those treated with warfarin and aspirin combination therapy, stroke reduction is lower than for
those on warfarin monotherapy, owing to the increased risk of haemorrhagic stroke. The rate of other
major bleeds is also higher, and NHS net savings are lower than on warfarin monotherapy (Table 7). More
details of the NHS cost impact are shown in Table 8.
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Strokes Bleeds QALYs NHS costs Social care costs
One-year impact -0.039 0.006 0.007 -£412 -£94
Lifetime impact -0.298 0.048 0.794 -£2,408 -£1,379
Treatment cost Excess major bleeds Averted strokes
One-year impact £139 £8 -£559
Lifetime impact £1,129 £66 -£3,603

Table 7: Estimated one-year and lifetime stroke, major bleed, QALY and cost impacts per person treated with warfarin
and aspirin combination therapy, relative to no antithrombotic therapy
treated with warfarin and aspirin combination therapy, relative to no antithrombotic therapy
Estimated clinical and cost impacts of GRASP-AF prescribing patterns
16. If it is assumed that the prevalence of AF and the distribution of CHA2DS2-VASc scores in England are
the same as the age-adjusted estimates from GRASP-AF, and prescribing patterns are also as in GRASP-AF,
it is estimated that 415,834 people with CHA2DS2-VASc score ≥ 2 were on warfarin in 2012-13. Of this
number, it is estimated that 356,086 were on warfarin monotherapy, and 59,748 were taking both
warfarin and aspirin. For a monotherapy group of this size, it is estimated that 13,906 strokes, including
3,801 fatal strokes, would be averted through warfarin in a year, and 106,231 strokes, including 29,449
fatal strokes, over a lifetime perspective. It is estimated that the number of deaths from all causes would
be reduced by 4,185 over a one-year perspective. The model predicts that there would be an additional
2,183 non-intracerebral bleeds in a year and 16,935 over a lifetime. Annual net savings to the NHS from
averted strokes are estimated at £147 million over one year, and £858 million over a lifetime perspective.
There are additional estimated savings to social care (Table 9). More details of the NHS cost impact are
shown in Table 10. Impacts for the warfarin and aspirin combination therapy cohort are shown in Tables
11 and 12.
Table 9: Estimated one-year and lifetime stroke, major bleed, QALY and cost impacts for a cohort of 356,086 people
Improving Quality
NHS
Results
13
One-year impact -0.037 0.011 0.006 -£379 -£92
Lifetime impact -0.284 0.081 0.754 -£2,181 -£1,305
One-year impact £145 £12 -£536
Lifetime impact £1,167 £100 -£3,448
One-year impact -13,906 2,183 2,330 -£146,747,063 -£33,450,628
Lifetime impact -106,231 16,935 282,892 -£857,627,384 -£490,997,377

Improving Quality
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Results
14
for a cohort of 356,086 people treated with warfarin monotherapy, relative to no antithrombotic therapy
treated with warfarin and aspirin combined therapy, relative to no antithrombotic therapy
Table 12: Estimated one-year and lifetime NHS cost impacts of treatment, major bleeds and averted strokes for a
cohort of 59,748 people treated with warfarin and aspirin combined therapy, relative to no antithrombotic therapy
17. Combining the results for warfarin monotherapy and warfarin and aspirin combined therapy, we
estimate that 16,137 strokes a year, including 4,396 fatal strokes, are averted in people with AF, on the
assumption that current prescribing patterns across England are as observed in GRASP-AF. The number
of excess major bleeds is estimated at 2,812 a year. Taking into account also the increased long-term risk
of death associated with disabling strokes, total deaths in people with AF who are taking warfarin (or
warfarin plus aspirin) are reduced by an estimated 4,820 over a one-year perspective.
Estimated clinical and cost impacts of NICE-recommended prescribing
18. If it is assumed that the prevalence of AF and the distribution of CHA2DS2-VASc scores in England are
the same as the age-adjusted estimates from GRASP-AF, and prescribing patterns are also as in GRASP-AF,
it is estimated that there were 710,938 people with CHA2DS2-VASc score ≥ 2 (excluding those on other
anticoagulants and those for whom anticoagulants are contra-indicated or declined). If all of this group
were taking warfarin, it is estimated that 27,763 strokes, including 7,589 fatal strokes, would have been
averted in 2012-13, and NHS costs associated with AF would have been reduced by £293 million over one
year and £1.7 billion over a lifetime perspective, relative to no anti-thrombotic therapy (Tables 13 and 14).
This represents an additional 11,626 strokes averted, and £124 million one-year cost reduction (£724
million over a lifetime perspective), relative to estimated current prescribing patterns.
One-year impact £49,581,481 £2,891,212 -£199,219,755
Lifetime impact £401,849,653 £23,432,788 -£1,282,909,825
One-year impact -2,232 629 369 -£22,645,716 -£5,506,964
Lifetime impact -16,939 4,841 45,032 -£130,331,196 -£77,984,729
One-year impact £8,659,694 £879,786 -£32,185,196
Lifetime impact £69,721,057 £7,083,345 -£207,135,598

Improving Quality
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Results
15
for a cohort of 710,938 people treated with warfarin monotherapy, relative to no antithrombotic therapy
Sensitivity analyses
19. It is known that the cost of INR management for people taking warfarin is subject to considerable
local variation. The Evidence Review Group for a 2012 NICE technology appraisal proposed that three
values for annual INR monitoring should be used in sensitivity analysis (£115.14, £241.54 and £279.36).29
In sensitivity analyses 1-3 we have used these values, updated to 2012-13 prices (£117.83 in sensitivity
analysis 1, £247.18 in sensitivity analysis 2, and £285.89 in sensitivity analysis 3).
20. In all three scenarios, the estimated net cost impact for the NHS is negative, meaning that estimated
savings from averted strokes exceed the cost of AF- associated treatment and monitoring. However, net
savings are lower than in the base case (Tables 15 and 16). With the highest estimated level of INR
monitoring costs, net annual savings to the NHS for care associated with AF are 43% lower than the
base case estimate over a one-year perspective, and 58% lower over a lifetime. Net social care costs
are unaffected.
Table 15: Sensitivity analyses 1-3: Estimated one-year and lifetime NHS cost impacts per person treated with
warfarin monotherapy, relative to no antithrombotic therapy, with annual INR monitoring costs of £115.14,
£241.54 and £279.36
One-year impact -27,763 4,359 4,651 -£292,985,574 -£66,785,332
Lifetime impact -212,095 33,811 564,803 -£1,712,282,662 -£980,293,204
One-year impact £98,991,138 £5,772,404 -£397,749,115
Lifetime impact £802,306,697 £46,784,371 -£2,561,373,729
Net NHS cost impact
Base case Sensitivity 1 Sensitivity 2 Sensitivity 3
One-year impact -£412 -£391 £270 -£234
Lifetime impact -£2,408 -£2,241 -£1,297 -£1,015

Improving Quality
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Results
16
Table 16: Sensitivity analyses 1-3: Estimated one-year and lifetime NHS cost impacts for a cohort of 710,938 people
treated with warfarin monotherapy, relative to no antithrombotic therapy, with annual INR monitoring costs of
£115.14, £241.54 and £279.36 per person treated
21. Another key area of uncertainty is the marginal cost of ongoing NHS care for people with AF who
have experienced strokes. A recent study reported that the mean annual cost of post-stroke care was
higher than that of pre-stroke care for all levels of stroke severity in people with AF.23
However, the
differences were not significant at the 95% level. In the light of this uncertainty, we did not include
ongoing NHS costs in our base case. In sensitivity analysis 4, we use the mean differences between
pre- and post-stroke care annual costs from this study, updated to 2012-13 prices (£413 for mild stroke,
£894 for moderate stroke, £3,270 for disabling stroke). Using these estimates of post-stroke costs, the
saving to the NHS for AF-associated care increases relative to base case by 26% over a one-year
perspective, and 64% over a lifetime.
Table 17: Sensitivity analysis 4: Estimated one-year and lifetime NHS cost impacts for warfarin monotherapy, relative
to no antithrombotic therapy, including estimated post-stroke NHS costs
Net NHS cost impact
Base case Sensitivity 1 Sensitivity 2 Sensitivity 3
One-year impact -£292,985,574 -£277,741,418 -£192,121,293 -£166,498,138
Lifetime impact -£1,712,282,662 -£1,592,879,823 -£922,243,388 -£721,545,000
Per person treated For 356,086 people For 710,938 people
One-year impact -£519 -£184,678,126 -£368,716,250
Lifetime impact -£3,939 -£1,402,582,163 -£2,800,303,680

Improving Quality
NHS
Discussion
17
Discussion
1. The estimates of AF-associated prescribing, expenditure and outcomes set out in this paper have
been based on extrapolations from the GRASP-AF dataset, which provides details of AF status, age,
gender, CHA2DS2-VASc score, prior stroke status and antithrombotic prescribing. The extract used for this
report covered patients in more than a thousand GP practices. These practices together provide care to
approximately 13% of the population of England. England-level estimates of prevalence have been
standardised to match the national age-distribution as recorded in ONS. GRASP-AF does not provide other
demographic data such as ethnicity or deprivation, and it has therefore not been possible to standardise
for these variables.
2. Estimates of the impact of prescribing on stroke incidence, QALYs and costs are estimated by means of
a Markov model. The outputs of such a model are highly sensitive to the parameters used. For this
reason we have aimed to set out details of parameters and sources transparently. These are summarised in
the Methods section, and further detail is provided in Appendix 1. We have also carried out sensitivity
analyses in areas where variable parameters are subject to particular uncertainty or variability.
3. Our analysis suggests that more than 900,000 people in England have AF (1.74%). Of this group,
around 84% have a CHA2DS2-VASc score ≥ 2 (a population prevalence of 1.46%). We estimate that
current levels of warfarin (or warfarin plus aspirin) treatment in this group are associated with prevention
of around 16,100 strokes a year, including 4,400 fatal strokes.
4. The number of excess major bleeds associated with warfarin, or warfarin plus aspirin prescribing for
this group is estimated at around 2,800 a year. (This excludes intracerebral bleeds, which are included in
the stroke estimate). Taking into account also the increased risk of death associated with disabling stroke
in those who have survived to 30-days, total deaths in people with AF are reduced by an estimated 4,800
over a one-year perspective. The absolute reduction in the one-year death rate for those on warfarin
monotherapy is estimated at 1.17%. The reduction in all-cause annual mortality associated with warfarin
has been estimated at 1.6% in meta-analysis.9
It is possible therefore that our model under-estimates the
reduction in deaths associated with warfarin prescribing.
5.Over a lifetime perspective, our model estimates that 0.30 strokes are averted and 0.79 QALYs gained
per person treated with warfarin.
6. Recent NICE guidelines recommend that patients with a CHA2DS2-VASc score ≥ 2 should be offered
anticoagulation therapy. However, only just over half (53.60%) of people with a CHA2DS2-VASc score ≥ 2
in our dataset are prescribed warfarin or other anticoagulants. For a further 8.74% of this group, it is
recorded that anticoagulants are contraindicated or declined. There may therefore be substantial numbers
of people with AF who would benefit from anticoagulation therapy but are not receiving it. Our model
suggests that if warfarin were prescribed for all those with a CHA2DS2-VASc score of ≥ 2, apart from
those for whom it is contraindicated or declined, approximately 11,600 further AF-related strokes,
including 3,200 fatal strokes, would be averted each year in England. There would be an additional 1,500
excess bleeds, and the total number of deaths in people with AF, over a one-year perspective, would be
reduced by a further 3,500.
7. Our analysis suggests that warfarin prescribing for people with AF is associated with a net reduction in
the cost to the NHS of AF-related care. This reduction arises because the saving through averted strokes
exceeds the costs of treatment and of associated major bleeds. The one-year saving to the NHS from
warfarin (or warfarin plus aspirin) prescribing at the levels shown in our dataset for those who have AF in
England is estimated at £169 million, and the lifetime saving at £988 million. If warfarin were prescribed
for all those with a CHA2DS2-VASc score ≥ 2, apart from those for whom it is contraindicated or declined,
the estimated saving to the NHS on AF-related care is £293 million over one year, and £1.7 billion over a
lifetime perspective. There are further estimated savings to social care.

Improving Quality
NHS
Discussion
18
8. There is uncertainty regarding the efficacy of aspirin on stroke prevention in AF. Meta-analysis findings
report a non-significant 19% reduction in stroke incidence (compared with a 64% reduction with
warfarin).9
NICE has recommended that aspirin monotherapy should not be offered solely for stroke
prevention to people with atrial fibrillation. In view of this recommendation, and the statistical uncertainty,
we have presented analysis of aspirin in a separate appendix. Based on a 19% reduction in stroke
incidence, we estimate that over a one-year perspective aspirin would be associated with a reduction in
stroke incidence of 0.015 per person treated, compared with 0.039 for warfarin. Estimated overall NHS
costs rise with aspirin treatment, owing to an increase in the proportion of strokes that are haemorrhagic,
an increase in other major bleeds, and an increase in the proportion of disabling strokes. In economic
parlance, warfarin dominates aspirin as a therapy for stroke prevention in AF.
9. The recent NICE guideline also recommends that anticoagulants should be considered for men with a
CHA2DS2-VASc score of 1. There is little evidence on baseline stroke risk in this group, or on the impact of
anticoagulation. We did not feel that the evidence base was sufficiently robust to support estimation of
costs and benefits for this group. Further clinical studies are needed on the potential for stroke reduction
through anticoagulation in this group.
10. New oral anticoagulants (dabigatran etexilate, rivaroxaban and apixaban) have recently been approved
by a number of international bodies, including NICE in England and Wales, for stroke prevention in
sub-groups of the AF population. In both cases the product cost is considerably higher than that of
warfarin. The manufacturers of these drugs state that there is no requirement for regular anticoagulation
testing for dose adjustment with these medications.
11. The GRASP-AF data extract used for our paper covered the period from November 2011 to July 2012,
and the NICE recommendations on these new agents were published toward the end of this period. Not
surprisingly, therefore, use of these agents in the period covered by our study was very low (approximately
0.22% of total anticoagulant use in people with CHA2DS2-VASc score ≥ 2). In this paper, therefore, we
have not modelled the cost or impacts of prescribing of the new oral anticoagulants. It is likely, however,
that in the future there will be a need for further study on the impact of these agents on stroke risk in the
AF population in England, and associated costs.
12. There is variation in the cost of warfarin monitoring, and these costs have a substantial impact on
overall net cost estimates. A recent NICE technology appraisal used three values for warfarin monitoring in
sensitivity analyses. The value used in our base case is drawn from study evidence, and is lower than the
values used by NICE. We have used the NICE values in our sensitivity analyses. For all of these values, we
estimate that warfarin is associated with a reduction in the NHS cost of AF-associated care.
13. Given the variation in the cost of such monitoring around the country, the overall cost
impact of warfarin prescribing will also vary from place to place. There may be potential in places where
costs are particularly high to provide monitoring services more efficiently, thus increasing the overall cost
effectiveness of treatment.
14. There is also a need for further study on the cost of warfarin monitoring in people with AF. Since the
cost effectiveness of medications is estimated with reference to the next best option, understanding the
true cost of warfarin is important not only for assessment of the costs and savings of warfarin itself, but is
also an important factor in determining the cost effectiveness of alternative medications.
15. It is hoped that this paper will provide a foundation for local analysis and decision-making on
antithrombotic prescribing in AF.

Improving Quality
NHS
Appendix1
19
Transition
probabilities
No antithrombotics
(baseline)
Warfarin Warfarin and
aspirin
Aspirin
(See Appendix)
Ischaemic stroke
(annual)
Primary 4.75%,
Secondary 9.38%
(Estimated by applying
CHA2DS2-VASc risks
(Friberg et al.11
), to
CHA2DS2-VASc
distribution in GRASP-AF)
Primary 1.44%,
Secondary 3.11%
(Relative risk reduction:
64% (Hart et al.9
),
adjusted for impact on
haemorrhagic stroke,
applied to baseline risks
estimated above.
As for warfarin Primary 3.81%,
Secondary 7.53%
(Risk reduction: 19%
non significant (Hart et al.9
)
applied to baseline risks
estimated above.
Haemorrhagic stroke
(annual)
0.19% Estimated by
applying ratio of
intracerebral haemorrhage
in warfarin and
non-warfarin patients in
Singer et al16
. to estimated
risk with warfarin shown
in cell below.
0.34% Overall rate of
intracranial bleeds
estimated by taking
weighted average from
16 studies cited in Lip et
al12
. (0.73%), proportion of
these that are intracerebral
estimated from Hart el al.14
(46%)
Hazard ratio 1.53,
relative to warfarin alone
(Steinberg et al.18
)
0.19% - Overall rate of
intracranial bleeds taken
from Flaker et al.34
(0.41%),
proportion that are
intracerebral assumed
as for warfarin
Other intracranial
bleeds
0.18% Estimated by
applying rate ratio for
intracranial bleed in
warfarin and non-warfarin
patients from Go et al.15
to
risk of intracranial bleed in
warfarin estimated by
taking weighted average
from 16 studies cited by Lip
et al.12
, and subtracting
estimated haemorrhagic
stroke risk for non-warfarin
patients
0.39% Overall rate of
intracranial bleeds
estimated by taking
weighted average from
16 studies cited in Lip et
al12
(0.73%), proportion of
these that are not
intracerebral estimated
from Hart et al.14
(54%)
Hazard ratio 1.53,
relative to warfarin
alone (Steinberg et al.18
)
0.22% - Overall rate of
intracranial bleeds taken
from Flaker et al.34
(0.41%),
proportion that are not
intracranial assumed as
for warfarin
Stroke severity for
strokes survived
beyond 30 days
(Combined ischaemic
and haemorrhagic)
60% disabling (Hart et
al.9
), of remainder
moderate:mild ratio
= 1:2.95 (Lin et al.24
)
60% disabling (Hart et al.9
),
of remainder
moderate:mild ratio =
1:2.95 (Lin et al.24
)
Assumed as for warfarin 65% disabling: (13%
reduction in disabling
strokes, 29% reduction in
non-disabling strokes
(Hart et al.9
)),
of remainder
moderate:mild ratio =
1:2.95 (Lin et al.24)
30-day ischaemic
stroke mortality
24% (Hylek et al.21
) 16% for INR <2 (62% of
total), 6% for INR ≥2
(Hylek et al.21
)
Assumed as for warfarin 15% (Hylek et al.21
)
Appendix 1
Table A1.

Improving Quality
NHS
Appendix1
20
Transition
probabilities
No antithrombotics
(baseline)
Warfarin Warfarin and
aspirin
Aspirin
(See Appendix)
30-day haemorrhagic
stroke mortality
Assumed as for warfarin 41% (Hart et al.14
) Assumed as for warfarin 15% (Hylek et al.21
)
30-day mortality,
other intracranial
bleeds
Assumed as for warfarin 29% (Hart et al.14
) Assumed as for warfarin Assumed as for warfarin
Excess major
extracranial bleed
(annual)
0 (reference) 0.3% increase relative
to no antithrombotics
(Hart et al.9
)
Hazard ratio 1.53,
relative to warfarin
alone (Steinberg et al.18
)
0.2% increase relative to
no antithrombotics
(Hart et al.9
)
Stroke mortality post
30-days (Combined
ischaemic and
haemorrhagic)
Disabling stroke: HR 14.3, relative to no stroke. Non-disabling stroke: no significant diﬀerence in mortality risk
relative to no stroke (De Caterina et al.22
)
Non-stroke mortality AF all-cause mortality rate estimated using RR all-cause mortality in AF 1.5 (men). 2.2 (women) (Stewart et al.5
)
and applied to ONS life tables by year of age, further adjusted to remove stroke mortality (Hylek et al.21
, De Caterina
et al.22
)
Table A1.2: Cost estimates and sources for Markov model
NHS costs Social care costs
Warfarin Annual cost: Medication = £54.75 (BNF), Management = £94.80 (Ali et al.20
Jowett et al.28
)
adjusted for inflation (PSSRU33
). Sensitivity analyses 1 – 3, Management costs: £117.83,
£247.18, £285.89 respectively (NICE29
)
Aspirin Annual cost: Medication = £6.19 (BNF26
)
Warfarin and
aspirin
Annual cost: Medication = £60.94 (BNF26
), Management = £94.80 (Ali et al.20
Jowett et
al.28
) adjusted for inflation (PSSRU33
)
Fatal stroke £3,312 (Luengo-Fernandez et al.23
), adjusted for inflation (PSSRU33
)
Disabling stroke First 90-day cost: £26,240 (Luengo-Fernandez et al.23
).
Sensitivity analysis 4: ongoing annual costs £3,270 (Luengo-Fernandez et al.23
),
adjusted for inflation (PSSRU33
)
Annualcost:£23,101
(Luengo-Fernandezetal.23
),
adjustedforinflation(PSSRU33
)
Moderate stroke First 90-day cost: £19,212 (Luengo-Fernandez et al.23
).
Sensitivity analysis 4: ongoing annual costs £894 (Luengo-Fernandez et al.23
), adjusted for
inflation (PSSRU33
)
Annualcost:£11,527
),
)
Mild stroke First 90-day cost: £3,683 (Luengo-Fernandez et al.23
).
Sensitivity analysis 4: ongoing annual costs £414 (Luengo-Fernandez et al.23
), adjusted for
inflation (PSSRU33
)
Annualcost:£1,020
),
)
Major intracranial
bleed (excluding
intracerebral)
£2,589 (NHS Reference Costs25
, HRGs AA23C-G)
Major extracranial
bleed
£1,092 (NHS Reference Costs25
HRGs FZ38G-P)

Improving Quality
NHS
Appendix2
21
Appendix 2
The impact of aspirin monotherapy on stroke risk in AF
1. There is uncertainty regarding the efficacy of aspirin in reducing stroke risk in AF. Meta-analysis
suggests that aspirin monotherapy may be associated with a 19% reduction in stroke risk.9
However, this
estimate did not reach statistical significance at the 95% level. Recent NICE guidelines on AF recommend
that aspirin monotherapy should not be offered solely for stroke prevention to people with atrial
fibrillation. Recent European Society of Cardiology (ESC) guidelines state that “The evidence for effective
stroke prevention with aspirin in AF is weak, with a potential for harm”.4
2. In this appendix, we provide estimates from the Markov model for the impact of aspirin on stroke and
major bleed incidence, on QALYs and on NHS costs.
3. The stroke impacts are estimated from the (non-significant) meta-analysis results. Care should be taken
in interpreting the aspirin results owing to the uncertainty surrounding the meta-analysis estimate.
4. The rate of intracranial bleeds is estimated at 0.41%.34
No studies were identified which estimated the
discrete rate of intracerebral bleeds in people with AF taking aspirin monotherapy. It was therefore
assumed that 46% of intracranial bleeds are intracerebral, as for warfarin. The rate of excess extracranial
bleeds (0.2%) was taken from Hart et al.9
5. Thirty-day ischaemic stroke mortality was estimated at 15%.21
The proportion of disabling strokes was
estimated at 65%, based on meta-analysis findings that disabling strokes are reduced by 13% and
non-disabling strokes by 29%, relative to no treatment.9
The annual cost of aspirin treatment (£6.19) was
taken from BNF.26
Further details of inputs to the Markov model are provided in Appendix 1, Tables A1.1
and A1.2.
6. The Markov model indicates that the number of strokes prevented per person treated is lower with
aspirin than with warfarin, and the QALY gain is lower, over both a one-year and lifetime perspective.
While the cost of treatment is very low, the model suggests that overall NHS costs rise with aspirin
treatment, while they fall with warfarin (Table A2.1). The increase in costs arises because of an increase in
the proportion of strokes that are haemorrhagic, an increase in other major bleeds, and an increase in the
proportion of disabling strokes. In economic parlance, warfarin dominates aspirin as a therapy for stroke
prevention in AF, producing greater health gain and higher net savings.
Table A2.1: Estimated one-year and lifetime stroke, major bleed, QALY and cost impacts per person treated with aspirin
monotherapy, relative to no antithrombotic therapy
7. If it is assumed that prescribing patterns are as in GRASP-AF, it is estimated that in 2012-13 there were
279,229 people with CHA2DS2-VASc score ≥2 receiving antiplatelet monotherapy. Table A2.2 sets out
estimated stroke, major bleed, QALY and cost impacts on the assumption that all these patients were
taking aspirin.
One-year impact -0.015 0.002 0.004 £55.62 -£23.55
Lifetime impact -0.108 0.020 0.339 £563.08 -£212.72

Improving Quality
NHS
Appendix2
22
Table A2.2: Estimated one-year and lifetime stroke, major bleed, QALY and cost impacts for a cohort of 279,229 people
treated with aspirin monotherapy, relative to no antithrombotic therapy
One-year impact -4,221 636 1,020 £15,530,401 -£6,574,742
Lifetime impact -30,268 5,680 94,572 £157,229,118 -£59,397,707

Improving Quality
NHS
References
23
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