STROKE AND ATRIAL
FIBRILLATION AND
THE ROLE OF THE NOAC
DR ABUL AZIM
CONSULTANT IN ELDERLY MEDICINE & STROKE
Stroke and AF
•
110-120,000 Strokes per year
•
>20,000 TIA per year
•
15-20% of all ischaemic strokes have underlying AF
•
AF related strokes tend to be severe and disabling with high
mortality.
Stroke and AF
High prevalence of AF – 1.2% - possible underestimate
1:4 individuals aged 40 years have a life time risk for
developing AF
In 2007, 6.3 million people in US, Japan and Europe were
living with diagnosed AF.
With an aging population now likely to double in 30 years.
Prevalence of AF increases with age:
0.5% at 50-59 years
Almost 9% at 80-89 years
Stroke and AF
AF associated with 5 fold increase in stroke risk
Risk of stroke same for all variants of AF
Cardioembolic stroke has a 30 day mortality of 25%
15% reduction in hospital admission due to AF related
strokes in the UK would save an estimated £30 million/year
Meta analysis of 29 trials show Warfarin reduced stroke by
64-70%
Also showed decreased mortality
Warfarin reduces the risk of stroke in AF
Warfarin better
Placebo better
AFASAK
SPAF
BAATAF
CAFA
SPINAF
EAFT
RRR = 64%
ARR = 2.7%
All trials
95% CI: 49 to 74%
100
50
0
–50
Relative risk reduction (%)*
–100
Error bars = 95% CI; *Relative risk reduction for all strokes (ischaemic and haemorrhagic)
8
Hart RG et al. Ann Intern Med 2007;146:857–67
Limited efficacy of aspirin in reducing the risk of stroke in
patients with AF
Aspirin better
Placebo better
AFASAK
SPAF
EAFT
ESPS II
LASAF
125 mg/d
125 mg QOD
UK-TIA
300 mg/d
1200 mg/d
JAST
RRR = 19%
ARR = 0.8%
95% CI: –1 to 35%
All trials
100
50
0
–50
Relative risk reduction (%)*
–100
Error bars = 95% CI; *Relative risk reduction for all strokes (ischaemic and haemorrhagic)
9
Hart RG et al. Ann Intern Med 2007;146:857–67
AF in Elderly
Percentage of stroke attributable to AF:
1.5% for patients in their fifties
2.8% for patients in their sixties
18.8% for patients in their seventies
23.9% for patients in their eighties
BAFTA Trial:
•
Patients >75 with AF
•
Stroke risk halved
•
No increased bleeding risk compared with Aspirin
Royal College of Physicians, Edinburgh UK Consensus
(March 2012)
Key recommendations:
Detection of AF must be improved; a national screening
programme should be introduced
Uptake of OAC must be increased and methods of engaging
patients in their AF management should be improved
Aspirin should not be used for stroke prevention
in AF
Stott DJ, Dewar RI et al. RCPE UK Consensus Conference, March 2012.
Stroke risk assessment for patients with AF
CHADS-2 Score
C
Congestive cardiac failure
1
H
Hypertension >140-90 or on treatment
1
A
Age > 75 years
1
D
Diabetes mellitus
1
S
Stroke/TIA
2
Annual stroke risk – CHADS-2
CHADS SCORE
STROKE RISK %
0
1.9
1
2.8
2
4.0
3
5.9
4
8.5
5
12.5
6
18.2
Anticoagulation therapy
Score
Risk
Anticoagulation
therapy
Considerations
0
Low
None or Aspirin
Aspirin daily
1
Moderate
Aspirin or Warfarin Aspirin daily or
raise INR to 2.03.0, depending on
patient preference
2 or greater
Moderate or high
Warfarin
Raise INR to 2.03.0, unless
contraindicated
CHA2DS2-VASc
Condition
Points
C
Congestive heart failure (or Left ventricular
systolic dysfunction)
1
H
Hypertension: blood pressure consistently above
140/90 mm/Hg (or treated hypertension on
medication)
1
A2
Age>75 years
2
D
Diabetes mellitus
1
S2
Prior stroke or TIA or thromboembolism
2
V
Vascular disease (e.g., peripheral artery disease,
myocardial infarction, aortic plaque)
1
A
Age 65-74 years
1
Sc
Sex category (i.e., female gender)
1
CHA2DS2-VASc – STROKE RISK %
CHA2DS2-VAS Score
Stroke Risk %
0
0
1
1.3
2
2.2
3
3.2
4
4.0
5
6.7
6
9.8
7
7.6
8
6.7
9
15.2
Anticoagulation
Score
Risk
Anticoagulation
Therapy
Considerations
0
Low
No antithrombotic therapy No antithrombotic therapy
(or Aspirin)
(or Aspirin 75-325 mg daily)
1
Moderate
Oral anticoagulant (or
Aspirin)
Oral anticoagulant, either
new oral anticoagulant drug
e.g., Dabigatran or well
controlled Warfarin at INR
2.0 – 3.0 (or Aspirin 75-325
mg daily, depending on
factors such as patient
preference)
2 or
greater
High
Oral anticoagulant
Oral anticoagulant, using
either a new oral
anticoagulant drug (e.e.,
Rivaroxaban or Dabigatran)
or well controlled Warfarin at
INR 2.0 - 3.0
HAS-BLED Score for bleeding risk on oral anticoagulation
in AF
Hypertension systolic >160
1
Abnormal renal function
1
Abnormal LFT
1
Age >65 years
1
Stroke in past
1
Bleeding history
1
Labile INR
1
Alcohol
1
Other drug
1
Score of 3 or more indicates increased 1 years bleed risks on
anticoagulation (risk for intracranial bleed, bleed requiring
hospitalisation on a Hg drop > 2g/L or that needs transfusion.
Dabigatran etexilate for the prevention of stroke
and systemic embolism in AF
NICE TA Appraisal Guidance 249
1.1 Dabigatran etexilate is recommended as an option for the
prevention of stroke and systemic embolism within its
licensed indication, that is, in people with nonvalvular atrial
fibrillation with one or more of the following risk factors:
•
Previous stroke, transient ischaemic attack or systemic
embolism
•
Left ventricular ejection fraction below 40%
•
Symptomatic heart failure of New York Heart Association
(NYHA) class 2 or above
•
Age 75 years or older
•
Age 65 years or older with one of the following: Diabetes
mellitus, coronary artery disease or hypertension.
Guidance
1.2 The decision about whether to start treatment with
Dabigatran etexilate should be made after an informed
discussion between the clinician and the person about the
risks and benefits of Dabigatran etexilate compared with
Warfarin. For people who are taking Warfarin, the potential
risks and benefits of switching to Dabigatran etexilate should
be considered in light of their level of international
normalised ratio (INR) control.
Rivaroxaban for the prevention of stroke and
systemic embolism in people with AF
NICE TA Appraisal Guidance 256
1.1 Rivaroxaban is recommended as an option for the
prevention of stroke and systemic embolism within its
licensed indication, that is, in people with nonvalvular atrial
fibrillation with one or more risk factors such as:
•
Congestive heart failure
•
Hypertension
•
Age 75 years or older
•
Diabetes mellitus
•
Prior stroke or transient ischaemic attack.
Guidance
1.2 The decision about whether to start treatment with
Rivaroxaban should be made after an informed discussion
between the clinician and the person about the risks and
benefits of Rivaroxaban compared with Warfarin. For
people who are taking Warfarin, the potential risks and
benefits of switching to Rivaroxaban should be considered in
light of their level of international normalised ratio (INR)
control.
Evidence with new oral anticoagulants
RE-LY and Dabigatran
ROCKET-AF and Rivaroxaban
ARISTOTLE and APIXABAN
DABIGATRAN – RELY Study
Compared Warfarin with Dabigatran in patients with AF
18,113 people randomised
Two doses used i) 150 mg bd ii) 110 mg bd
Dabigatran 110 mg bd – non inferior to Warfarin
Dabigatran 150 mg bd – statistically significantly more effective than
Warfarin at reducing stroke and systemic embolism
Rates of major bleeding:
2.71%/yr low dose Dabigatran
3.11%/yr high dose Dabigatran
3.36%/yr for Warfarin
A non statistically significant reduction all cause mortality.
Both doses non statistically significant increased risk of myocardial
infarction.
DABIGATRAN – RELY Study
Both doses of Dabigatran shows statistically significant
reduction in incidence of haemorrhagic stroke compared
with Warfarin
Both doses shows statistically significant fewer life
threatening bleeds compared with Warfarin
Both doses associate with significantly higher rate of gastro
intestinal bleeding compared with Warfarin.
Dabigatran 150 mg bd associated with significantly higher
incidence of major gastrointestinal bleeding and also life
threatening gastrointestinal bleeding.
RIVAROXABAN – ROCKET-AF Trial
Compared Rivaroxaban with Warfarin in patients with AF
140,009 were enrolled
Rivaroxaban was demonstrated to be non-inferior compared
to Warfarin
Significant reduction in rate of fatal bleed with intracranial
haemorrhage with Rivaroxaban compared with Warfarin
Higher rate of gastrointestinal bleed
Concerns with Warfarin
Need for regular monitoring and have blood tests etc.
Frequent dosage adjustment
Slow onset of action
Drug and food interactions
Impact on people’s work, social and family life
Concerns with NOACs
Lack of long term safety data
Lack of specific antidote
Renal failure or impaired renal function and also the risk of
acute decline in renal function due to acute illness like
dehydration, shock, initiation of nephrotoxin medication.
Compliance and difficult to monitor compliance
Concerns with NOACs
Some concern with increased risk of MI
Higher risk of GI bleeding
Rivaroxaban cannot be dialysed
Expense and cost pressure
Advantage with NOAC
No need for monitoring INR and hence more patient friendly
In Warfarin intolerant patients
In patients difficult to control INR - TTR <60%
Useful for rapid anticoagulation following TIA in certain high
risk groups.
Advantage with NOAC
Patients suffering stroke/TIA despite being on Warfarin
(Dabigatran 150 mg bd)
Again, Dabigatran 150 mg bd more effective than Warfarin
in preventing stroke
Fewer drug and food interactions
Reduced risk of intracranial haemorrhage in both
SUMMARY
Patients with AF at high risk of disabling stroke
Following risk satisfaction more patients should be
anticoagulated as opposed to using Aspirin
Warfarin – well established with proven efficacy
Scope/role of the NOAC in certain patient groups. However,
should be used with caution because of some concerns.