Evidence based management of atrial fibrillation
Transcript of Evidence based management of atrial fibrillation
PROTECTPreventing AF-related stroke
GREGORY Y H LIP MD FRCP (Lond Edin Glasg) FACC FESC FEHRA
Price-Evans Chair of Cardiovascular Medicine, University of Liverpool, UK
National Institute for Health Research (NIHR) Senior Investigator
Distinguished Professor, Aalborg University, Denmark
Adjunct Professor, Yonsei University, Seoul;
Adjunct Professor, Seoul National University, South Korea.
………………………………………………………………………………..
©Prof GYH Lip
Declaration of Interests
• Guideline membership/reviewing: ESC Guidelines on Atrial Fibrillation, 2010 and Focused
Update, 2012; ESC Guidelines on Heart Failure, 2012; American College of Chest Physicians
Antithrombotic Therapy Guidelines for Atrial Fibrillation, 2012; NICE Guidelines on Atrial
Fibrillation, 2006 and 2014; NICE Quality Standards on Atrial Fibrillation 2015; ESC
Cardio-oncology Task Force, 2015; ESC Working Group on Thrombosis position documents
(2011-). Chairman, Scientific Documents Committee, European Heart Rhythm Association
(EHRA). Chairman, 2018 CHEST guidelines from American College of Chest Physicians
• Steering Committees/trials: Includes steering committees for various Phase II and III studies,
Health Economics & Outcomes Research, etc. Investigator in various clinical trials in
cardiovascular disease, including those on antithrombotic therapies in atrial fibrillation, acute
coronary syndrome, lipids, etc.
• Editorial Roles: Editor-in-Chief (clinical), Thrombosis & Haemostasis; Associate Editor,
Europace; Guest Editor, Circulation, American Heart Journal.
• Consultant/Advisor/Speaker:
– Consultant for Bayer/Janssen, BMS/Pfizer, Verseon, Boehringer Ingelheim, and Daiichi-
Sankyo.
– Speaker for Bayer, BMS/Pfizer, Boehringer Ingelheim and Daiichi-Sankyo
Contribution of AF to Incidence and Outcome of
Ischemic Stroke Population-Based L’Aquila StudyMarini et al Stroke 2005;36(6):1115-9.
Kaplan–Meier estimates of the
likelihood of recurrent stroke in
patients with and without AF
Annual Mortality Rates in Patients
With and Without AF:
At 1 year, AF 49.5% vs no AF,
27.5%
Increased mortality even up to 8 years
Recurrent stroke
Years after first stroke
Cu
mu
lati
ve
pro
bab
ilit
y
of
recu
rren
ce,
%
10
12
AF
No AF
8
6
4
2
00 2 4 6 8 10
P = 0.0398
Years post-stroke
Patients with AF
Patients without AF
An
nu
al m
ort
alit
y r
ate,
%
0
10
20
30
40
50
60
1 2 3 4 5 6 7 8
Mortality
Decision-making
interventions to stop
the global AF-related
stroke tsunami Cerasuolo … Lip et al
Int J Stroke 2017, 12(3) 222–228
(a) % population estimated to be alive
(65%), injured/ disabled (10%), and
dead (25%) within 30 days after the
2004 Boxing Day Tsunami in Aceh
Province.
(b) % AF patients without prior OAC
estimated to be alive and without
disability (25%), disabled (50%), and
dead (25%) 30 days after an AF-
related stroke.
(c) % AF patients receiving warfarin with
an INR > 2 estimated to be alive and
without disability (49%), disabled
(42%), and dead (9%) 30 days after an
AF-related stroke
Proportion alive, dependent, and dead in the Boxing
Day Tsunami and after an AF-related stroke with
and without prior anticoagulant treatment
The CHA2DS2-VASc score Lip et al Chest. 2010;137:263-72
Camm, Kirchhof, Lip et al
Eur Heart J 2010; 31, 2369–2429
CHA2DS2-VASc for
stroke in Asians with AFKorean Nationwide Sample
Cohort Study
Kim … Joung, Lip.
Stroke 2017 DOI:
10.1161/STROKEAHA.117.016926
Patients who were
categorized as low
risk consistently had
an event rate <1%
per year.
Event rates for different outcomes for non-
anticoagulated AF patients with less than 2 Non-
Gender Related stroke risk factors Fauchier … Lip. Stroke 2016 DOI: 10.1161/STROKEAHA.116.013253
0
1
2
3
4
5
Low risk
[CHA2DS2-
VASc 0 in males,
1 in females]
1 risk factor
[CHA2DS2VASc
1 in males; 2 in
females]
2.62(1.16-5.89)
3.21(1.11-9.26)
2.82 (1.32-6.04)
3.88 (2.51-6.0)
4.69 (1.88-11.6)
4.20(2.24-7.86)
Adjusted
HREv
ent
rate
%/y
ear
CHA2DS2-VASc Scores of
Patients With AF
±Ischemic Stroke:
Baseline, Follow-Up, Delta Chao, Lip et al
J Am Coll Cardiol. 2018;71(2):122–32.
Risk stratification and thromboprophylaxis made easy Lip and Lane Circ J 2014 June; Griffiths and Lip Circulation 2014;130(21):1837-9
Patient with atrial fibrillation
STEP 1 Is the patient 'low risk'?
'Low risk'’ = CHA2DS2-VASc score = 0 (male) or 1 (female)
STEP 2
Offer stroke prevention if ≥1 additional stroke risk factors*
NOAC VKA (eg. warfarin)
with Time in Therapeutic Range (TTR) >70%
If yes ...
No antithrombotic therapy
VKA, Vitamin K Antagonist
NOAC, non-Vitamin K
antagonist oral anticoagulant
.
* Use the HAS-BLED score to identify patients at ‘high risk’ of bleeding for more careful
review and followup, and to address reversible risk factors for bleeding. A high HAS-BLED
score (≥3) does not preclude use of OAC, and may help with NOAC dose selection
• CHA2DS2-VASc best to identify ‘low risk’
• Even 1 CHA2DS2-VASc factor confers risk of stroke
and death
• The NCB is +ve for OAC even with 1 stroke risk factor
How to apply guidelines into clinical practice
The default is stroke prevention*
unless ‘low risk’
*Stroke prevention means oral anticoagulation, whether as
well managed warfarin with good TTR or NOAC
10
The ‘3 –step’ [PS. It’s not a dance routine]
…. to streamline decision-making pathway for stroke
prevention in patients with atrial fibrillationLip et al. Thromb Haemost 2017; 117: 1230–1239
Step 2 Consider stroke
prevention (ie. oral
anticoagulant) in all AF
patients with ≥1 additional
stroke risk factors*
No
antithrombotic
treatment
SAMe-TT2R2 score >2Regular review/INR
checks/counselling for VKA
users
… or try a NOAC
SAMe-TT2R2 score 0–2Consider VKA treatment
(eg, warfarin)
*Calculate the HAS-BLED score. If HAS-BLED ≥3, address the modifiable
bleeding risk factors and ‘flag up’ for regular review and follow-up.
Calculate
SAMe-TT2R2 score
Low stroke risk
CHA2DS2-VASc
score:
0 in males
1 in females
Step 3
Decide on NOAC or
VKA with high time in
therapeutic range
Step 1 Identify low-
risk patients
The ‘3 –step’ [PS. It’s not a dance routine]
…. to streamline decision-making pathway for stroke
prevention in patients with atrial fibrillationLip et al. Thromb Haemost 2017; 117: 1230–1239
Step 2 Consider stroke
prevention (ie. oral
anticoagulant) in all AF
patients with ≥1 additional
stroke risk factors*
No
antithrombotic
treatment
SAMe-TT2R2 score >2Regular review/INR
checks/counselling for VKA
users
… or try a NOAC
SAMe-TT2R2 score 0–2Consider VKA treatment
(eg, warfarin)
*Calculate the HAS-BLED score. If HAS-BLED ≥3, address the modifiable
bleeding risk factors and ‘flag up’ for regular review and follow-up.
Calculate
SAMe-TT2R2 score
Low stroke risk
CHA2DS2-VASc
score:
0 in males
1 in females
Step 3
Decide on NOAC or
VKA with high time in
therapeutic range
Step 1 Identify low-
risk patients
Streamlining primary and secondary care
management pathways for stroke
prevention in AFCollaborative working and application of the simple
‘Birmingham 3-step’ approach Lip, Lane, Sarwar. Eur Heart J. 2017;38(40):2980-2982.
13
http://guidance.nice.org.uk/CG/Wave0/638/Consultation/Latest
…. the initial clinical decision step should use
the CHA2DS2-VASc score to determine the low
risk patients who do not require
antithrombotic therapy.
‘Low risk’ patients are defined as those with a
CHA2DS2-VASc score=0 if male, or a score=1,
if female.
Subsequent to this step, stroke prevention
should be offered to those AF patients with one
or more stroke risk factors.
Anticoagulation
Control and
Prediction of
Adverse Events in
Patients With
Atrial Fibrillation
Wan et al
Circ Cardiovasc Qual
Outcomes. 2008;1:84-91
For retrospective studies, a 6.9%
improvement in the TTR
significantly reduced major
hemorrhage by 1 event per 100
patient-years of treatment (95%
CI, 0.29 to 1.71 events).
TTR negatively correlated with major
hemorrhage (r=-0.59; P=0.002) and
thromboembolic rates (r=-0.59;P=0.01).
How to best identify those
patients who would do well on
VKA with high TTR?
0
1
2
3
4
5
6
7
8
Ou
tco
me
even
ts r
ate
(per
10
0 p
atie
nt-
yea
rs, %
)
0 40 50 60 70 80 90
TTR (%)
Major haemorrhage
Thromboembolic
Linear (Major haemorrhage)
Linear (Thromboembolic)
Stroke/SERE-LY 0.66 (0.53–0.82)
ROCKET AF 0.88 (0.75–1.03)
ARISTOTLE 0.80 (0.67–0.95)
ENGAGE AF 0.88 (0.75–1.02)
Combined (random) 0.81 (0.73–0.91)
Major bleeding
RE-LY 0.94 (0.82–1.07)
ROCKET AF 1.03 (0.90–1.18)
ARISTOTLE 0.71 (0.61–0.81)
ENGAGE AF 0.80 (0.71–0.90)
Combined (random) 0.86 (0.73–1.00)
Secondary efficacy and safety outcomes
Efficacy Ischaemic stroke 0.92 (0.83–1.02)
Haemorrhagic stroke 0.49 (0.38–0.64)
MI 0.97 (0.78–1.20)
All cause mortality 0.90 (0.85–0.95)
Safety ICH 0.48 (0.39–0.59)
GI bleeding 1.25 (1.01–1.55)
Efficacy and safety of 4 high dose NOACs vs
warfarin: meta-analysis of phase III trialsRuff CT, et al. Lancet 2014;383:955–62
GI, gastrointestinal; ICH, intracranial haemorrhage; MI, myocardial infarction NOAC, non-VKA oral anticoagulant; SE, systemic embolism
There have been no head -to-
head studies between NOACs.
Conclusions about the relative
efficacy or safety of any the
NOACs cannot be drawn
from these data.
Favours NOAC
0.5 1.0
Favours warfarin Favours NOAC
0.5 1.0 2.0
Favours warfarin
Favours NOAC
0.2 0.5 2.0
Favours warfarin
1.0
2.0
Evolving Changes of the Use of Oral
Anticoagulants and Outcomes in Patients with
Newly-Diagnosed Atrial FibrillationChao .. .. Lip, Chen. Circulation 2018
The initiation rates
of OACs in newly
diagnosed AF
patients significantly
increased from
13.6% to 35.6%,
contemporaneous
with the introduction
of NOACs.
A lower risk of
ischemic stroke and
mortality was
temporally
associated with the
increasing
prescription rates of
OACs.
Oral Anticoagulation in Very Elderly Patients
with AF- A Nationwide Cohort Study Chao .. .. Lip Circulation 2018 10.1161/CIRCULATIONAHA.117.031658
Risks of ischemic stroke and ICH were compared between
11,064 AF and 14,658 non-AF patients aged ≥90 years
without antithrombotic therapy from year 1996 to 2011.
Oral Anticoagulation in Very Elderly Patients
with AF- A Nationwide Cohort Study Chao .. .. Lip Circulation 2018 10.1161/CIRCULATIONAHA.117.031658
From year 2012 to 2015, 768 AF patients aged ≥90
years treated with warfarin and 978 patients
treated with NOACs (dabigatran in 361,
rivaroxaban in 557 and apixaban in 60)
Risk of dementia in stroke-free patients diagnosed with
atrial fibrillation: data from a population-based cohort Kim .. Lip, Joung. Eur Heart J 2019 doi:10.1093/eurheartj/ehz386
Incident AF
was associated
with an
increased risk
of dementia,
independent of
clinical stroke
in an elderly
population.
OAC use was
linked with a
decreased
incidence of
dementia.
NICE guidelines (2014) …
led to the development of
NICE menu indicators,
which were adopted into the
Quality and Outcomes
Framework (QOF).
Use bleeding risk
assessment appropriately
and responsibly
• Bleeding risk assessment is to address
modifiable bleeding risk factors
• Then flag up ‘high risk’ patients for
early review and followup with a
bleeding risk score
• Bleeding risk is highly dynamic
• High bleeding risk score is not an
excuse to withhold OAC
– This is an education and
implementation issue
Patient-Centered Outcomes Research Institute
(PCORI) review ‘.. .. .. HAS-BLED provides the
best prediction for bleeding risk’
Patient with Atrial Fibrillation;
Eligible for Oral Anticoagulation
Identifies ‘at risk’ patients for more regular review and follow-up
For patients with an increased risk of bleeding the benefit of OAC usually, but not always, outweighs the bleeding risk; thus, regular review and careful monitoring of bleeding risk is important
Do not withhold OAC solely because the patient is at risk of falls
EHR and ‘electronic alerts’
Low risk=No action
High risk=Patient ‘flagged up’ for review
A ‘high risk’ bleeding risk score is not a
reason or excuse to withhold OAC
Review and address potentially reversible bleeding risk factors
- Uncontrolled hypertension
- Labile INRs (if on VKA)
- Concomitant use of aspirin and NSAIDs in anticoagulated patient
- Alcohol excess
Bleeding risk assessment
Bleeding Risk
Assessment in
AF: Observations
on the Use and
Misuse of
Bleeding Risk
Scores
Lip and Lane.
J Thromb Haemostat 2016
DOI: 10.1111/jth.13386.
We need a holistic approach to detection and improving
management of patients with AF
The patient pathway
… integrated care for managing atrial fibrillation
in a holistic manner
Cardiovascular risk factors & associated comorbidities
Symptoms? Rate control or rhythm control?
Stroke prevention
Real world
management
requires simple
and practical
decision making
processes
Improve
detection
of AF
A holistic approach to risk assessment and
management of patients with atrial fibrillation?
Secondary careNon-Cardiologists; Cardiologists (Non-AF vs AF)
Patients with AF
Primary Care
Awareness and improved
detection of atrial
fibrillation; allowing early
intervention
A holistic and integrated
approach to management
of AF patients
Patients with AF present to
GPs (often asymptomatically),
emergency rooms, non-
cardiologists (perioperatively,
ICU), cardiologists (non-
arrhythmia specialists and
arrhythmia specialists)
… and our AF patients need
a simple, streamlined
uniform and practical
approach to their care and
management
‘The patient pathway …’
‘The patient journey …’
The Atrial
Fibrillation Better
Care (ABC)
pathway for
integrated care
management
‘B’ Better symptom
management
Treat symptoms
‘Birmingham 3-step
Patient-centred and symptom-directed
decisions on rate versus rhythm control
• Manage hypertension, heart failure,
diabetes mellitus, cardiac ischaemia, and
sleep apnoea
• Lifestyle changes: obesity reduction,
regular exercise, and reduction of
alcohol and stimulant use
• Patient psychological mobidity
• Consider patient values and preferences
Step 1
• Identify low-risk patients
Step 3
• Decide on OAC (either a
VKA with well-managed
TTR or a NOAC
Step 2
• Offer stroke prevention
to patients with one or
more risk factors for
stroke
• Assess bleeding risk
‘A’ Avoid stroke
Optimise stroke
prevention
‘C’ Cardiovascular
and other
comorbidities
Manage risk factors
The Atrial fibrillation Better Care (ABC)
pathway for integrated management provides
a simple strategy that that streamlines primary
and secondary care of patients with AF.
The Atrial fibrillation Better Care (ABC) PathwayLip. Nat Rev Cardiol 2017 doi:10.1038/nrcardio.2017.153
Primary Care
Clinical Pathway
March 2018
CHA2DS2-VASc
HAS-BLED
SAMe-TT2R2
The ABC
of
Atrial Fibrillation
management
Detect, Protect, Perfect elements:• Detect more cases of AF,
• Protect with Anticoagulation and
modification of other CV risk factors
• Perfect the quality of therapy by
ensuring that patients are monitored
and followed up appropriately
https://bit.ly/2FhrwXQ
Integrated care management of patients with AF and risk of CV
events: The ABC (Atrial fibrillation Better Care) pathway in the
ATHERO-AF study cohort.Pastori .. .. Lip Mayo Clin Proc 2018 DOI: 10.1016/j.mayocp.2018.10.022
Multivariate modelHR for
MACE95% CI p value
‘ABC’ pathway
management0.44 0.24 0.80 .007
Female sex 0.62 0.42 0.91 .02
Paroxysmal AF 0.91 0.63 1.31 .59
Age ≥75 years 2.17 1.49 3.15 <.001
Prospective single-center cohort study including 907 consecutive patients with non-valvular
AF on VKAs from February 2008 to December 2016. Median followup 37 months
A, B and C groups were defined as follows:
• “A” by a Time in Therapeutic Range ≥65%; “B” by a European Heart Rhythm Association
(EHRA) symptom scale I-II; “C” as optimized cardiovascular comorbidity management.
• Primary endpoint was a composite outcome of CVEs.
HR 0.40, 95%CI 0.22-0.74
Integrated care
management of patients
with AF and risk of CV
events: The ABC pathway
in the ATHERO-AF study
Pastori .. Lip. Mayo Clin Proc 2018
DOI: 10.1016/j.mayocp.2018.10.022
Univariate model
HR for
CVEs
(95%CI)
p
value
Incidence rates
(%/year, 95%CI)p value
Study
groups
Control
groups
‘A’ group
(vs. TiTR<65%)
0.51
(0.35-0.75).001
2.7
(1.9-3.6)
5.2
(4.1-6.5)<.001
‘B’ group
(vs. EHRA III-IV)
0.58
(0.39-0.86).007
3.4
(2.7-4.2)
6.1
(4.3-8.6).003
‘C’ group
(vs. comorbidities)
0.38
(0.26-0.58)
<.00
1
2.1
(1.5-3.0)
5.5
(4.4-6.8)<.001
‘ABC’ group
(vs. any of ‘non-A’,
‘non-B’ or ‘non-C’)
0.40
(0.22-0.74).003
1.8
(0.9-3.0)
4.5
(3.7-5.5).001
AF confers a large healthcare burden from stroke
Stroke and bleeding risks are dynamic, and regular reassessment is needed.
Stroke prevention means oral anticoagulation, whether as VKA with high TiTR or
NOAC
Increase awareness and detection of AF in high risk groups
The default is stroke prevention unless ‘low risk’
– Use the simple, practical ‘3-step’ …. to streamline decision-making for stroke
prevention in AF
Additional decision steps should consider ....
- Symptom management, with regards to decisions on rate control or rhythm
control
- Cardiovascular and comorbidity risk management
Stroke prevention should be part of a proactive, integrated approach to
management of AF ... which can be simple as ABC
PROTECTPreventing AF-related stroke