Establishing peer-consensus for the optimal anticoagulation
treatment in the ageing population with NVAF A Prescriber
supplement commissioned and sponsored by Daiichi Sankyo UK
Ltd
CURRENT THINKING
2 A Prescriber publication 2021
Background Atrial fibrillation (AF) is the most com- monly
sustained cardiac arrhythmia, with an increasing prevalence due to
improved survival rates from conditions such as ischaemic heart
disease (IHD) as well as an expanding ageing population.1
AF that does not result from a mechanical heart valve or mitral
stenosis is often referred to as nonvalvular AF or NVAF. One in
four middle-aged adults in Europe will develop AF and this is
expect- ed to rise sharply in the future. Estimates suggest an AF
prevalence of approx- imately 3% in adults aged 20 years or older,
with greater prevalence in older persons and in patients with
conditions such as hypertension, heart failure, coro- nary artery
disease (CAD), valvular heart disease, obesity, diabetes mellitus,
or chronic kidney disease (CKD).2
AF presents a significant risk if untreated If left untreated, AF
is a significant risk factor for stroke and other morbidities such
as thromboembolism. In particular, AF is associ- ated with a 3- to
5fold increased risk of ischaemic stroke, and the attributable risk
of stroke associated with AF increases from 1.5% in subjects aged
50 to 59 years of age to 23.5% among those aged 80 to 89 years. Up
to 30% of ischaemic stroke patients have AF diagnosed before,
during or after the initial event.1-4
In the occurrence of stroke, the presence of AF is associated with
greater severity of stroke and increased risk of early death com-
pared with non-AF.5,6
Costs of AF and stroke are significant In 2016, the overall burden
of management of patients with AF with/without an ischae-
mic stroke/major bleeding event would relate to an annual cost
between £9,000- 18,000, this equates to total annual direct cost to
the NHS of between £8.1 and £16.2 billion.1 In 2015, the average
cost of a stroke per person was £45,409 in the first 12 months
after stroke (cost of incident stroke), plus £24,778 in subsequent
years (cost of preva- lent stroke). Stroke is a principle cause of
disa- bility in the UK, with almost two thirds of sur- vivors in
England, Wales and Northern Ireland leaving hospital with a
disability.7,8 The aver- age cost of NHS and Personal Social
Services (PSS) care in the first year after a severe stroke is
almost double that for a minor stroke (£24,003 compared to
£12,869). Of the NHS and PSS costs, the cost attributed to
NHS-funded care is £3.4 billion.7
Effective stroke prevention in NVAF Anticoagulation remains the
single inter-
Establishing peer-consensus for the optimal anticoagulation
treatment in the ageing population with NVAF
Authors
Bakhai A, Royal Free Hospital, London Batt T, Aneurin Bevan
University Health Board (Retired), Wales Beale K, University
Hospitals Birmingham NHS Foundation Trust, Birmingham Chelliah R,
University Hospitals of Leicester, Leicester Guyler P, Southend
University Hospital Trust, Southend Kankum P, Kent & Medway
CCG, Kent Kavia K, Manor Medical Centre, Thurmaston Mashru V, East
Leicestershire and Rutland Clinical Commissioning Group, Leicester
Prescott C, University Hospitals Dorset, Dorset
Declarations of interest AB: clinical trials for var. pharma and
device partners, incl. Roche; scientific advice and educational
services to Roche and other companies. TB, KB, VM: no declarations.
RC: no conflicts. PG: travel grants, conference and/or speaker fees
from pharma compa- nies involved in DOAC therapies, incl. Daiichi
Sankyo, Boehringer Ingelheim, Bayer, BMS Pfizer; principal
investigator for NIHR-ap- proved clinical trials funded by some of
these companies, but no direct financial interest from these. PK:
travel grants from Daiichi Sankyo. KK: speaker fees: Amgen,
AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi
Sankyo, Eli Lilly, GlaxoSmith- Kline, Novartis, Novo Nordisk,
Pfizer, Sanofi; Diabetes Professional Care publication(s): Novo
Nordisk; advisory boards: Amgen, Bristol-Myers Squibb, Daiichi
Sankyo, Pfizer, Eli Lilly; research grants/funding: Bristol-Myers
Squib, Pfizer, Daiichi Sankyo, Novo Nordisk. CP: consultancy work
with Bayer and BMS-Pfizer.
CURRENT THINKING
3A Prescriber publication 2021
vention which can mitigate the risk of stroke; a leading cause of
disability and mortality.9,10 If patients are given the correct
treatment, anticoagulation can prevent most ischaemic strokes in
patients with AF and prolong life.2 Oral anticoagulants (OACs) such
as vitamin K antagonists (VKA) have been commonly used but over the
last decade direct oral anticoagulants (DOACs, sometimes called
novel oral anti- coagulants or NOACs) have been intro- duced as a
more convenient, fixed-dose alternative. Compared with VKA, DOAC
therapy avoids the need for regular labora- tory monitoring of
patients by international normalised ratio (INR) testing due to a
wider therapeutic window, allows once (edox- aban, rivaroxaban) or
twice (apixaban, dab- igatran) daily intake and is associated with
fewer drug–drug interactions.9 The practi- cal aspects of a DOAC
are important and include convenience, frequency of dosage and the
need to take with or without food. European Society of Cardiology
(ESC) guidelines (2016) state: When oral antico- agulation is
initiated in a patient with AF who is eligible for a DOAC
(apixaban, dab- igatran, edoxaban or rivaroxaban), a DOAC is
recommended in preference to a vitamin K antagonist.2
The risk of all-cause mortality is lower with DOACs compared with
warfarin and the risk of major or intracranial bleeding is reduced
with most of the DOACs relative to warfarin, although the DOACs are
asso- ciated with substantial non-neurological bleeding
risk.10
Despite the publication of numerous guidelines on AF management, a
substan- tial proportion of eligible patients are undertreated
(Figure 1).11,12 Antico ag- ulation can significantly reduce the
risk of stroke and though some doctors have been reluctant to
prescribe these drugs because of concerns about bleeding, for most
people this benefit (stroke risk reduction) outweighs the
risks.12
Ageing patients with AF Patients with NVAF are at increased risk of
both stroke and bleeding events as they
age2–4, making treatment particularly com- plex. Many clinicians
continue to underuse anticoagulation in those elderly patients
(i.e. filtered by chronological age alone) who could benefit from
it. Although clinical experience with the DOACs is limited compared
to that of warfarin, sub- group analyses demonstrate the relative
merits of DOACs in the treatment of the latter cohort.12
A significant number of stroke patients are below 70 years of age
(Figure 2), suggesting that the term ‘elderly’ is of limited use in
defining this patient cohort; there is a need to consider other
factors such as the presence of comorbidities and complexities when
assessing stroke risk and appropriate preventative interven- tions.
Approximately 73% of all stroke patients in the UK have at least
one comor-
bidity, and 13% have three or more (Figure 3). Regardless of
‘elderly’ status, these patients could be considered to be part of
an ‘ageing’ NVAF population.15
Age is not the only proxy in determining risks associated with
NVAF. The authors agreed the following definition of ageing
patients with NVAF:
Patients with NVAF living with, and developing, comorbidities and
medical complexity as they age16
Objectives The objectives of this project are to under- stand the
attitudes of clinicians from across the UK and define a clear
consensus from a large sample of respondents. This will provide
clarity on the specific consid- erations required in the approach
to NVAF management in ageing patients and the optimal use of OACs
in stroke prevention. In pursuing these objectives, this group
intends to understand attitudes and identify challenges within it
so that clear calls-to-action may be defined. This may help to
support alignment between the views of various roles and regions of
the
The prevalence of AF increases with age and occurs in 6% of the
over 65 population.14
Figure 1. Percentage of patients in AF receiving anticoagulation
treatment13
The percentage of patients with AF receiving anticoagulation
treatment by age group for the period April 2017 to March 2018.
Adapted from: Healthcare Quality Improvement Partnership. Sentinel
Stroke National Audit Programme (SSNAP). Clinical audit April 2013
– March 2018 Annual Public Report. National Results. June 2019.
SSNAP applies to England, Wales and Northern Ireland.
40
30
20
10
0
UK and inform practice in managing NVAF in ageing patients.
Methodology A UK expert-steering group met in October 2019 to
review the current land- scape and identify key topics in the NVAF
care pathway through discussion. The key topics agreed were: 1.
Differing complexities of patients with
NVAF (Table 2) 2. Prescribing considerations (Table 4) 3. NVAF
monitoring (Table 6)
4. Anticoagulation service delivery (Table 7)
5. Education and counselling (Table 8) 6. Research (Table 9)
These topics were each further discussed in order to generate
consensus statements that reflected the group’s thinking, for
testing across a wider audience of healthcare profes- sionals
(HCPs) involved in NVAF care. Consen- sus statements (n=40) were
identified (see Appendix), these statements were construct- ed to
provide insight into the use of anticoag-
ulants in UK practice. The statements were collated into a
questionnaire, which was sent to HCPs (Geriatricians,
Cardiologists, Emer- gency Physicians, GPs, Nurses, Pharmacists,
Heads of Medicine Management (HoMM) and Clinical Commissioning
Group (CCG) Commissioners) who identified themselves as being
involved in the care of patients with NVAF. Respondents were
engaged by an independent agency using a third party data- base. No
honorarium was provided for com- pletion of the questionnaire. The
group wished to compare any pat- terns of response from different
roles and regions of the UK, so the questionnaire cap- tured role
and geographic region. Respondents were offered a 4-point Lik- ert
scale to rate their agreement with each statement, ranging across
‘strongly disagree’, ‘tend to disagree’, ‘tend to agree’ and
‘strongly agree’. Completed questionnaires were collat- ed and the
individual scores for each state- ment analysed in order to produce
an arith- metic agreement score for each. The responses were broken
down further by role and UK region in order to identify variances
in the respondent’s agreement scores. The majority of responses
were from England (313/371; Table 1). The steering group (A Bakhai,
T Batt T, K Beale, R Chelliah, P Guyler, P Kankum, K Kavia, V
Mashru, C Prescott – see author details for affiliations)
predefined the threshold of agreement for consensus at 70% and
over. Consensus was defined as ‘high’ at ≥70% and ‘very high’ at
≥90%. Further rounds of ques- tionnaire distribution were
considered; how- ever, due to the high levels of agreement with all
but two of the 40 statements, the group elected to work with the
original responses to the statements.
Results Completed questionnaires were returned by 371 UK
respondents and analysed to define the total level of agreement
with each of the 40 statements. Figure 4 and Table 1 summa- rise
the demographics of the respondents. Tables 2, 4 and 6–9 show the
40 statements and the consensus score for each one. The scores are
also summarised in Figure 5.
35
30
25
20
15
10
5
Age breakdown (years)
(% )
Figure 2. Age profiles of stroke admissions and discharges in the
UK (Jan-Mar 2020)
16.0
10.1
15.1
Figure 3. Comorbidity profiles of stroke admissions and discharges
in the UK (Jan-Mar 2020)
Adapted from: Healthcare Quality Improvement Partnership. SSNAP
Portfolio for January–March 2020 admissions and discharges. July
2020.15 SSNAP applies to England, Wales and Northern Ireland.
35
30
25
20
15
10
5
Number of comorbidities
5A Prescriber publication 2021
Discussion Respondents agreed that ageing patients represent those
who are not actively anticoagulated due to the presence of risk
factors such as advanced age, the presence of one or more
comorbidities or those at a high risk of falls (Statement 1, 71%).
• The HAS-BLED17 score is used to assess
major bleeding risk in patients with AF and includes age >65
years as a contributor to overall risk of bleeding.
• The exclusion of ageing (elderly and/or complex) patients from
many clinical trials can limit best clinical practice (State- ment
3, 81% agreement), it is therefore mportant to extrapolate relevant
data from clinical studies including real world evi- dence
(RWE).
• There was no overall consensus regarding a lack of clinical
guidelines for ageing patients with NVAF being a limiting factor
for best clinical practice; this may be due to differ- ences in
perception of the term ‘ageing’ or potential variations in
practice.
Analysis of this question based on role shows that no specific role
group achieved consen- sus agreement for this statement and the
lowest agreement was among geriatricians with an agreement score of
33%, this sug- gests that specialists in treating NVAF may be more
cognisant of guidelines or more com- fortable in applying best
practice in their absence. HCPs strongly agree that evidence should
be applied in making treatment deci- sions (Statement 4, 92%
agreement) and that
those classed as complex are best managed by specialist
multidisciplinary team (MDT) (Statement 5, 80% agreement). All
groups agreed that a lack of confidence in the HCP may deem some
patients to be seen as com- plex (Statement 6, 81% agreement)
indicat- ing perhaps that HCP education regarding AF may be needed
for some specific roles (HoMM and Nurses provided the strongest
agreement to this statement of 86% and 83%, respectively). There
was also clear agreement that complex patients with NVAF may not
always receive appropriate anticoag- ulation. Primary Care
practitioners may focus on onward referral for complex patients (as
t h e a v e r a g e p r i m a r y c a r e practitioner may not see
many patients with AF annually) whereas ambulatory care patients
may be afforded greater consideration and would be actively
monitored by hospital specialists. ESC and NICE guidance are seen
as key in the UK, but community HCPs may not be as familiar with
differentiating or supporting data as specialists. The NHS Long
Term Plan18 prioritises the prevention of strokes through
anticoagula- tion of patients with AF; this will become even more
important as the UK population ages. If a decision is made not to
anticoagu- late a patient then that patient will be at greater risk
of stroke with potentially greater healthcare resource need and
costs to the wider health system (e.g. care costs, drug costs,
social care costs, loss of employment). The decision not to
anticoagulate a patient should therefore be made in conjunction
with a specialist MDT. Even when best practice is adopted and
anticoagulation is recommended, poor ad herence to treatment will
result in lack of adequate stroke prevention. Adherence in ageing
patients is challenging due to the greater incidence of
comorbidities such as dementia and poor mobility. It is recommended
to use CHA2DS2- VASc19 and HAS-BLED to assess risk along- side
other factors (including adherence) when considering treatment for
the age- ing population with NVAF. It should be noted that the
HAS-BLED score was not
Table 1. Respondents by UK region
Group Number of respondents (n)
England (North) 77
England (South or South West exc. London) 70
England (London) 79
n= 9
n= 14
n= 71
n= 66
n= 40
n= 81
n= 37
n= 53
CURRENT THINKING
6 A Prescriber publication 2021
designed to avoid or stop anticoagulation but to assess/modify risk
of bleeding. It is important that these patients are reviewed at
least annually (and more frequently as need-
ed) with each identified risk factor addressed. When selecting a
DOAC for use in ageing patients, it is recommended that: •
Randomised Controlled Trial (RCT) data be
extrapolated for this population; • Chronological age,
co-morbidities (includ-
ing polypharmacy) and frailty are consid- ered;
• Differences in mechanism of action and the potential implications
for drug metabolism and drug-drug interactions should always be
considered.
The high level of agreement of all state- ments in this section
provides a strong base to make recommendations regarding pre-
scribing considerations, although response to Statement 12 was at
the threshold of con- sensus. Analysis of responses to Statement 12
reveals some variation, the highest level of agreement was from
Pharmacists (83.1; n=71) and the lowest was from Geriatricians
(42.5%; n=40). Optimal persistence and adherence are a key factor
in preventing strokes using oral anticoagulants. In this context,
some HCPs m ay c o n s i d e r d o s i n g re g i m e n s relevant.
A meta-regression of persistence to cardiac medications confirmed
that people on twice-daily dosages are 23% less likely to have good
persistence than those with once-daily regimes, and a US study
(n=36,868) comparing DOACs noted higher likelihood of suboptimal
adherence for twice-daily dosing with apixaban or dabiga- tran
(combined), than for once - daily dosing with edoxaban or
rivaroxaban (combined).25 Counselling for DOACs should be based on
stroke prevention rather than treatment to assist in achieving
adherence as patients are often asymp tomatic and less inclined to
adhere to regular DOAC use.26
When considering an appropriate DOAC treatment, ageing patients
with NVAF may require: • As simple a routine as possible (such
as
once-daily dosing) • The ability to take a DOAC with or
without
food; this is important in patients who have erratic eating habits
(i.e. patients with dementia)
• Considerations around potential poor vision
• Considerations around poor dexterity • Considerations around
cognitive
function and memory (including carer
100
90
80
70
60
50
40
30
20
10
0
Figure 5: Consensus Scores by Statement
NOTE: Green horizontal line represents the 70% threshold for
consensus agreement, red line shows the 33% agreement level, the
blue line indicates the threshold for very high consensus
(90%).
Table 2. Differing complexities of patients with NVAF
No: Topic: Statement: Score %
1 Differing complexities of patients with NVAF
Ageing patients with NVAF are those who are within licence, but not
actively anticoagulated due to concerns about potential risk (e.g.
due to age, comorbidity or those at a high risk of fall)
71%
2 Ageing patients with NVAF do not fit into current clinical
guidelines and this can limit best clinical practice
50%
3 Best clinical practice can be limited due to the fact that many
trials exclude complex and ageing patients in their study
population
86%
4 All patients with AF should be managed according to available
evidence
92%
5 Complex patients with AF are best managed via a specialist
MDT
80%
6 A lack of confidence of behalf of the HCP can deem some patients
to be seen as complex
81%
7 A significant number of complex patients do not receive
appropriate anticoagulation
77%
support levels) • Patient education and close monitoring to
ensure good adherence Data from ETNA-AF-Europe32 n= 13,092) and the
European cohort of ENGAGE AF-TIMI 4833 (n= 3322) respectively,
demonstrates
that compared with warfarin, edoxaban is associated with a lower
incidence of major bleeding (1.05% vs 2.15%); a similar rate of
all-cause mortality (3.50% vs 3.46%); a lower incidence of
CV-mortality (1.63% vs 2.47%) (see Figure 6).
ETNA-AF-Europe provides further evidence for the use of edoxaban in
ageing patients; the mean age of patients complet- ing 1-year
follow up was 73.6 years, rising to 79.5 years among patients who
received a dose reduction.31
Increased risk of falling is indepen- dently associated with an
elevated risk for major bleeding, fractures caused by a fall, and
mor- tality in ageing anticoagulated patients. A pre-specified
analysis of ENGAGE AF-TIMI 48 found that compared with warfarin,
edox- aban has demon- strated a greater absolute risk reduction in
severe bleeding events (ARR, –141 events/10,000 patient-years [95%
CI: –272 to –10]) and all-cause mortality (ARR, –66 [95% CI: –331
to +199]) in these patients.34 Frailty levels, comorbidity
profiles, poten- tial drug–drug interactions and age should all be
considered when selecting a DOAC. One- year safety results appear
to support the safety profile of edoxaban in routine clinical
practice and reinforce the results previously reported in
randomised-controlled trials. Edoxaban should therefore be
considered an appropriate treatment for ageing patients with NVAF.
There was strong agreement for each statement in this topic (92–97%
agreement) demonstrating the importance of monitor- ing DOAC
patients within 3 months of initia- tion and then at least annually
for non-com- plex patients. More complex patients
Table 3. Impact of CYP metabolism in patients with comorbidities
who are on polypharmacy – features of current DOACs.
Dabigatran20 Rivaroxaban20,21 Apixaban20,22 Edoxaban23,24
Target IIa (thrombin) Xa Xa Xa
Hours to Cmax 1.25-3 2-4 3-4 1-2
CYP metabolism None 66% Yes <1%
Bioavailability ~6.5% ~90% ~50% for doses up to 10mg ~62%
Transporters P-gp P-gp/BCRP P-gp/BCRP P-gp
Protein binding 35% in humans 92-95% in humans 87% in humans 55% in
vitro
Half-life 12-14 h 5-13 h ~12h 10-14 h
Renal elimination 80% 33% 27% 50%
Table 4. Prescribing considerations
No: Topic: Statement: Score %
8 Prescribing considerations
When considering potential DOAC options, consideration should be
given to dosing regimen
96%
9 When considering potential DOAC options, consideration should be
given to adherence
99%
10 When considering potential DOAC options, consideration should be
given to frailty levels
89%
11 When considering DOAC options, consideration should be given to
the safety profile
98%
12 When considering potential DOAC options, consideration should be
given to age
70%
13 When considering potential DOAC options, consideration should be
given to a patient’s comorbidities
96%
14 When considering potential DOAC options, consideration should be
given to a patient’s counselling needs
85%
15 When considering potential DOAC options, consideration should be
given to a patient’s monitoring needs
89%
8 A Prescriber publication 2021
(including ageing patients) may require more frequent monitoring,
particularly during any intercurrent condition likely to impact on
renal and/or liver function. Where specialist resource to monitor
patients is in limited supply, there may be utility in the use of
the wider healthcare team including HCAs and pharmacy technicians.
Any personnel undertaking monitoring of patients taking a DOAC
should have a clear understanding of any ‘red flags’ that would
require rapid referral to specialist support. Patients should be
reviewed within 1 month of DOAC initiation in ageing patients or
soon- er if the patient makes contact with the healthcare provider.
In some instances, patients can be reviewed online or via tele-
phone or videoconference using different toolkits including
questionnaires. The COVID-19 pandemic is having a sig- nificant
impact on the UK and it is important that consideration is given to
protecting vul- nerable patients, including the need for shielding
and the impact on the HCP deliver- ing care. There is a need for
the NHS to risk-stratify patients with NVAF and prioritise
monitoring; the NHS must ensure prescribing decisions are informed
by available evidence for the ageing population with NVAF. NHS
England guidance35 (March 2020) in light of COVID-19 recommends
that DOACs should be initiated, if possible, instead of warfarin to
minimise the monitoring burden and that remote consultations to
initiate anticoagu-
lant therapy and provision of follow-up by telephone be used, where
possible. All statements in this section achieved consensus (70–98%
agreement). There was agreement that cost is a consideration when
choosing a DOAC in the UK (Statement 22, 70%), but responses to
this statement may differ in other health economies. Respondents
agree that DOACs should be regarded as the standard of care for
anti- coagulation in NVAF. It was agreed by respondents that
pharmacy and nursing staff are currently under utilised in
monitoring patients; services should consider how these
roles are best deployed to achieve good out- comes for the patient
and the NHS. To support the wider use of different roles in
managing patients with NVAF (including the primary/secondary care
inter- face) providers should consider the use of an integrated
care pathway (ICP) for ageing patients with NVAF seen in Primary
Care as this would be helpful to commission NVAF services against.
An ICP may also help to reduce variations in care and support audit
activity. In general, respondents feel confident in initiating and
managing DOAC treatment
Table 5. Clinical outcomes of DOACS vs. warfarin in patients ≥75
years27
DOAC (Study) N. patients
Dabigatran 110 mg/ 150 mg (RE-LY)28
7,258 Median 2.0 Stroke/ SEE D110 vs. W: HR 0.88 (0.66-1.17) D150
vs. W: HR 0.67 (0.49-0.90)
D110 4.4% yr / D150 5.1% yr vs. W 4.4% yr D110 vs. W: P=0.89 D150
vs. W: P=0.07
Rivaroxaban 20 mg vs. warfarin (ROCKET AF)29
6,229 2 Stroke/ SEE HR 0.80 (0.63-1.02) 4.9% yr vs. 4.4 % yr HR
1.11 (0.92-1.34)
Apixaban 5 mg (ARISTOTLE)30
5,678 1.8 Stroke/ SEE HR 0.71 (0.53-0.95) 3.3%yr vs. 5.2 %yr
P<0.05
Edoxaban 60 mg (ENGAGE AF)31
8,474 2.8 Stroke/ SEE HR 0.83 (0.66-1.04) 4.0% yr vs. 4.8% yr
P<0.05
HR, hazard ratio; OR, odds ratio; RR, risk reduction; SEE, systemic
embolic event; W, warfarin.
5.0
4.0
3.0
2.0
1.0
0.0 Incidence of Rate of all-cause Incidence of major bleeding
mortality cardiovascular mortality
P ec
en ta
g e
o f
p at
ie nt
)
Figure 6. Bleeding and mortality outcomes for patients treated with
edoxaban and warfarin32,33
ETNA-AF-Europe (n=13,092)
1.05
2.15
9A Prescriber publication 2021
in patients with NVAF, however , there was a clear difference of
opinion regarding com- plex patients (Statement 35, 67%). Special-
ist respondents (Geriatrician, Cardiologist)
are confident in managing complex patients (98% and 86% agreement,
respec- tively) but other roles (Nurse, Pharmacist, HoMM, Emergency
Physician) did not
achieve consensus in their individual responses (45%, 52%, 54%, 57%
agree- ment, respectively). This difference is per- haps to be
expected; it is logical that those in roles who have the greatest
experience of prescribing DOACs in NVAF would be more confident in
doing so. It is encourag- ing that GPs achieved consensus agree-
ment with Statement 35 (72% agreement) although there is some
variation given the response to Statement 23 (There is a cohort of
ageing patients with NVAF who are not anticoagulated in Primary
Care but should be; 85% agreement), which is supported by the
evidence base1 that suggests approxi- mately 15% of patients with
AF are not pre- scribed anticoagulants in Primary Care. Data from
SSNAP15 (January–March 2020, n=21,379) reports that 19% of UK
stroke patients had an existing AF diagnosis on admission to
hospital and a further 6% received a diagnosis during their
hospital admission; this suggests that approximate- ly a quarter of
patients with AF are undiag- nosed prior to a stroke. The majority
of diag- nosed pat ients were prescr ibed anticoagulant medication
with 76% receiv- ing a DOAC and 24% a VKA. The INR of those
patients prescribed a VKA varied sig- nificantly with 38% within
the broadly opti- mal 2–3 range.36 Primary care prescribers should
have confidence in both initiation and repeat prescription of DOACs
in ageing patients but with appropriate referral for the most
complex cases. The Primary Care Network (PCN) should refer to the
Secondary Care link (i.e. anti-coagulation MDT representa- tive) as
needed. Evidence is emerging regarding the safety of using DOACs in
age- ing patients and clinicians should consider the safety
profiles of individual DOAC treat- ments when making prescribing
decisions. Respondents agreed that education and counselling should
be accessible and ongoing. In response to COVID-19, it is
anticipated that this will move to virtual delivery over time.
Those patients who can- not access virtual methods (particularly
relevant in ageing patients) may require individualised
plans.
Table 6. NVAF Monitoring
No: Topic: Statement: Score %
16 NVAF Monitoring
Within 3-months after DOAC initiation, all patients should be
reviewed to ensure correct dosing
92%
17 All DOAC patients should be monitored at least annually in line
with NICE guidance
97%
18 Some patients, including those deemed complex, require more
frequent monitoring
94%
19 Access to timely specialist advice should be available for all
DOAC patients when required
96%
No: Topic: Statement: Score %
20 Anticoagulation service delivery
All DOAC patients should know which HCP to contact when
required
98%
21 An interruption to DOAC therapy may require MDT support
73%
22 Cost is a consideration when choosing an appropriate DOAC
70%
23 There is a cohort of ageing patients with NVAF who are not
anticoagulated in Primary Care but should be.
86%
82%
25 Choice of anticoagulation treatment should not be determined by
commissioning arrangements
81%
26 DOACs should be the standard of care for anticoagulation in
NVAF
91%
27 Pharmacy has an under-utilised role in the monitoring of
anticoagulation patients at present
83%
28 Nursing has an under-utilised role in the monitoring of
anticoagulation patients at present
74%
29 An integrated care pathway for ageing patients with NVAF seen in
Primary Care would be helpful to commission NVAF services
against
96%
10 A Prescriber publication 2021
There was strong agreement with all three statements in this topic,
confirming the importance and relevance of RWE in informing
practice in NVAF. Regarding DOACs, RWE studies may vary greatly in
design and outcomes; large multi-centre studies may provide the
most robust data to add to the evidence base. Age is not the only
factor in determin- ing risks associated with NVAF, for exam- ple,
a fit and healthy 85 year old may be associated with lower bleeding
and stroke risks than a younger but frailer individual. The
Rockwood score37 gives a score ofclinical frailty but is not
helpful in isolation. The HAS-BLED score is used to determine major
bleeding risk, the
CHA2DS2-VASc calculates stroke risk for patients with AF. Due to
the significance of a stroke to the patient, if there is a risk of
stroke, neither the Rockwood nor HAS- BLED scores should be reasons
NOT to anticoagulate a patient with NVAF. Anti- coagulation can
significantly reduce the risk of stroke and though some doctors
have been reluctant to prescribe these drugs because of concerns
about bleed- ing, for most people this benefit (stroke risk
reduction) greatly outweighs the risks.12
Conclusion NVAF is a significant risk factor for stroke and
thromboembolism, both of which are
associated with significant patient impact (including mortality)
and costs to the wider health system. The use of anticoag- ulants
in patients with NVAF has been established in common medical
practice for many years; more recently, the devel- opment of DOACs
has provided a more convenient, fixed-dose alternative to VKA with
reduction in major bleeding, in par- ticular intracranial
hemorrhage. Despite these recent advances there are a number of
patients who are currently undertreat- ed. This consensus project
was established to understand the attitudes of HCPs towards NVAF
treatment (and specifically DOACs in ageing/complex patients) in
the UK and to provide a set of recommenda- tions to inform practice
regarding the opti- mum anticoagulation treatment in the ageing
population with NVAF. Responses from 371 HCPs involved in the
management of NVAF demonstrated agreement with 95% (38/40) of the
state- ments developed by the steering group. Two statements did
not achieve consensus threshold (Statements 2 and 35). The response
to Statement 2 (Ageing patients with NVAF do not fit into current
clinical guidelines and this can limit best clinical practice; 50%)
could be due to specialists being most comfortable with relevant
guidelines and best practice compared to other roles (i.e.
pharmacist, nurse, CCG commissioner), or it may be that there is an
element of ambiguity in the use of the term ‘ageing patients’; a
universal defini- tion of this cohort of patients would be useful
when discussing best practice. Statement 35 (I feel confident in my
ability to initiate DOAC use in complex patients; 67%) also did not
achieve consensus, and the response levels between roles indicate
that specialist roles (geriatrician, cardiolo- gist) achieved
consensus agreement and whereas non-specialist roles achieved lower
levels of agreement. The high levels of consensus provide a strong
platform for the recommendations made by the steering group and
support the role of DOACs in the anticoagulation of ageing patients
with NVAF. These recom-
Table 8. Education & Counselling
No: Topic: Statement: Score %
30 Education & Counselling
Access to counselling should be available for all DOAC patients
when required
96%
31 Both NVAF patient education and DOAC counselling should be
ongoing
89%
32 I feel confident in my ability to initiate DOAC use in
general
86%
33 I feel confident in my ability to continue prescribing of DOACs
in general
86%
34 I feel confident in my ability to monitor DOACs in general
86%
35 I feel confident in my ability to initiate DOAC use in complex
patients
67%
36 I feel confident in my ability to continue prescribing of DOACs
in complex patients
70%
37 I feel confident in my ability to monitor DOACs in complex
patients
75%
No: Topic: Statement: Score %
38 Research Real world evidence (RWE) should be proactively
collected about the use and monitoring of DOACs
96%
39 Collecting RWE can support continuity of care of NVAF in an
ageing population
97%
40 Collecting RWE will support the knowledge base to improve NVAF
care in an ageing population
97%
11A Prescriber publication 2021
mendations are offered in order to provide guidance on the
appropriate use of DOACs in a cohort of ageing patients who may
currently be under treated and therefore at risk of stroke.
Recommendations The following recommendations are offered based on
the learnings identified through the consensus exercise : 1. An
ageing patient is defined as: A patient with NVAF living with, and
devel- oping, comorbidities and medical complexity as they age 2.
The following criteria should be assessed by the non-specialist to
identify and con- sider the ageing patient with NVAF: • Renal
function (creatine clearance) • Age and weight (dosing) • Drug-drug
interactions (polypharmacy) • Frailty and fall risk • Previous GI
bleed and history of peptic
ulcers. • History of IHD and potential need for
concurrent antiplatelet treatment • CHA2DS2-VASc/HAS-BLED Score •
Other lifestyle factors (diabetes, social
history, use of NSAIDs) • Alcohol use 3. Non-specialists should be
able to initiate DOACs (or know where to refer) in Primary Care and
should consider the following: • Is there a clinical reason not to
anticoag-
ulate an ageing patient with NVAF? • DOACs are preferable over
warfarin in
ageing patients with NVAF where no exclusion criteria exist
4. Choice of a DOAC should be proactively considered with ageing
patients and prac- tical factors are important such as: • Age •
Frailty • Co-morbidities • Eating patterns • Adherence/persistence
• Dosing • Polypharmacy and potential drug–drug
interactions
• Side-effect profile 5. A DOAC should be selected with evi- dence
that substantiates its choice in the ageing patient cohort and
edoxaban should be considered as an option for treating ageing
patients with NVAF. 6. A specialist MDT should be organised
(according to locality) and these ageing patients should be
referred to the MDT and regional networks.
Limitations As with all surveys, potential limitations of this
study include the way in which the questions were worded and the
order in which they were asked, and how respond- ents were
approached. However, the questions were constructed by the steer-
ing group who also ratified the final form of the questionnaire
before distribution. There was no specific representation from GPs
on the steering group, this would have been useful in order to draw
out any specific issues relating to the role of the
50
40
30
20
10
INR at arrival to hospital
P er
ce nt
(% )
Figure 7. AF diagnosis and medication status of stroke patients in
the UK (Jan-Mar 2020)15
Of those with existing AF diagnosis, 66% were prescribed an
anticoagulant
Of those receiving anticoagulant treatment, 76%
were prescribed a DOAC
Of those receiving VKA treatment, 38% had an International
Normalised Ratio (INR) of 2–3 on arrival at hospital
Adapted from: Healthcare Quality Improvement Partnership. SSNAP
Portfolio for January - March 2020 admissions and discharges. July
2020.15
New diagnosis on admission to hospital 6%, n=1190
Existing AF diagnosis 19%, n=4072
No existing AF diagnosis 75%, n=16,117
Antiplatelet only 8%, n=342
Neither medication 26%, n=1069
Anticoagulant and antiplatelet medication 3%, n=137
Anticoagulant only 62%, n=2,524
DOAC 75%, n=2480
42 38
CURRENT THINKING
12 A Prescriber publication 2021
GP in managing NVAF. There was a strong response from England
(313/371) compared with other regions (other parts of the UK). The
overall results were therefore heavily influenced by practice in
England. That said, comparison of responses between England and
other regions did not show any significant variation in attitude to
the consensus statements. This consensus was focussed specifically
on clinical opinion with a view to defining and recognising the
issues attached to anti- coagulation in ageing patients with NVAF.
Patient experience has not been captured, this may help to further
the understanding of NVAF and anticoagulation from the patient
perspective and the optimal approach to pre- vention of strokes in
these patients. It is hoped that this consensus review may act as a
springboard to raise the issue of anticoagulation in ageing
patients and con- tribute to the evidence base to support the
Primary Care prescribing of DOACs in patients with NVAF.
Summary The results of the consensus have pro vided a strong
indication of the atti- tudes of clinicians to the use of DOACs in
the prevention of strokes in a patient cohort that may be under
prescribed in Primary Care. The steering group were able to form a
strong set of recommendations with the aim of clarifying the role
of Pri- mary Care in managing a greater number of ageing patients
with NVAF optimally
with DOACs. This consensus review should be repeated in 5 years to
assess changes in practice and define more appropriate
recommendations at that time.
References 1. Bakhai A, et al. J Eval Clin Pract 2020;27:119–33. 2.
Kirchhof P, et al. Eur Heart J 2016;37:2893–962. 3. NICE. Atrial
fibrillation: management [CH180].
https://www.nice.org.uk/guidance/cg180/ chapter/Introduction
[Accessed 02 July 2020]. 4. Wolf PA et al. Stroke1991;22:983–8. 5.
Kimura K, et al. J Neurol Neurosurg Psychiatry 2005;76:679–83. 6.
Henninger N, et al. Stroke 2016;47:1486–92. 7. Stroke Association.
Current, future and avoidable costs of stroke in the UK. Executive
summary Part 2. October 2017. 8. Adamson J, et al. J Stroke
Cerebrovasc Dis 2004;13:171–7. 9. Maura G, et al. BMJ Open
2019;9(4):e026645. 10. López-López JA, et al. BMJ 2017;359:j5058.
11.Marzec LN, et al. J Am Coll Cardiol 2017; 69:2475–84. 12. Foody
JM. Clin Interv Aging 2017;12:175–87. 13. Healthcare Quality
Improvement Partner- ship. Sentinel Stroke National Audit Programme
(SSNAP). Clinical audit April 2013–March 2018 Annual Public Report.
National Results. June 2019. 14. Feinberg WM, et al. Arch Intern
Med 1995;155:469–73. 15. Healthcare Quality Improvement Partner-
ship. SSNAP Portfolio for January – March 2020 admissions and
discharges. July 2020. 16. Guyler, P. Presentation at UK Stroke
Forum, 7th December 2020. Prevention better than
cure: Addressing health inequalities to improve stroke prevention
during COVID-19. 17. Pisters R, et al. Chest 2010;138:1093–100. 18.
NHS. The NHS Long Term Plan. January 2019. 19. Lip GY, et al. Chest
2010;137:263–72. 20. Eriksson B, et al. Clin Pharmacokinet
2009;48:1–22. 21. Xarelto Summary of Product Characteristics. 22.
ELIQUIS Summary of Product Characteristics. 23. LIXIANA Summary of
Product Characteristics. 24. Parasrampuria DA, Truitt KE. Clin
Pharmacokinet 2016;55:641–55. 25. Alberts MJ, et al. Int J Cardiol
2016;215:11–3. 26. Horne R, et al. PLoS One 2013;8:e80633. 27.
Cavallari I, Patti G. Anatol J Cardiol 2018;19:67–71. 28. Eikelboom
JW, et al. Circulation 2011; 123:2363–72. 29. Halperin JL, et al.
Circulation 2014;130:138–46. 3 0 . H a l vo r s e n S , e t a l .
Eu r H e a r t J 2004;35:1864–72. 31. K ato E T, et al . J Am Hear
t Assoc 2016;5:e003432. 32. de Groot JR, et al. Eur Heart J
Cardiovasc Pharmacother 2020; pvaa079. 33. de Groot JR, et al.
Poster P4756. Presented at European Society of Cardiology Congress
2019, Paris, France; 31st August – 4th September 2019. 34. Steffel
J, et al . J Am Coll Cardiol 2016;68:1169–78. 35. NHS England.
Clinical guide for the man- agement of anticoagulant services
during the coronavirus pandemic. 31 March 2020. 36. Lip GY, et al.
BMJ 2002;325:1022–5. 37. Rockwood K, et al. CMAJ
2005;173:489–95.
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Date of preparation: July 2021 EDX/21/0629