New Guidelines on Stroke Prevention for Atrial

Fibrillation – Europe, Far East or USA, Nice or not?

The Asia Pacific Heart

Rhythm Society Guidelines
Hung-Fat Tse, MD, PhD
Chair, Professor of Cardiovascular Medicine
William MW Mong Professor in Cardiology
The University of Hong Kong
Queen Mary Hospital
Hong Kong

Venice Arrhythmias 2015

 Venice Arrhythmias 2105

MY CONFLICTS OF INTEREST ARE

- Scientific Advisory Board: St. Jude Medical,

Boston Scientific; Medtronic
- Scientific Research: St. Jude Medical, Boehringer
Ingelheim; MSD, Bayer; Sanofi; GSK; BMS Pfizer;
Boston Scientific; Medtronic
- Speaker’s Bureau: St. Jude Medical, Boehringer
Ingelheim; MSD, Bayer; Sanofi; GSK; BMS Pfizer;
Boston Scientific; Medtronic, Daiichi
 Guidelines for AF

2013
1989

2000

2005

2009

2011
2014

2014 AHA/ACC/HRS
RCT 2014 NICE
2014 AAN
Warfarin
? Aspirin

Ximelagatran

Clopidogrel
Dabigatran
Rivaroxaban
Apixaban
Edoxaban
2014 AHA/ASA
2013
2013 JCS

2012
2012 ESC Focused Updates
2012 CCS Focused Updates
2012 APHRS
2011 2012 ACCP
2012 AHA/ASA
2010
2006 2011 CCS
2011 ACCF/AHA/HRS
2010 ESC Focused Updates
2006 ACC/AHA/ESC 2010 JCS
2006 NICE
 Do we need an additional
guidelines for Asia-Pacific region?
•  ? Ethnic differences on prevalence
of AF
•  ? Stroke risk related to AF in Asia-
pacific populations
•  ? Differences in the risk and benefit
of anticoagulation therapy for stroke
prevention
 Do we need an additional
guidelines for Asia-Pacific region?
•  ? Ethnic differences on prevalence
of AF
•  ? Stroke risk related to AF in Asia-
pacific populations
•  ? Differences in the risk and benefit
of anticoagulation therapy for stroke
prevention
 Prevalence of AF
East vs. West
18 18
Framingham

Men Women Western Australia

Prevalence of Atrial Fibrillation (%)

16 16 Rochester

Prevalence of Atrial Fibrillation (%)

Iceland
14 14 ATRIA study
Rotterdam study
12 12
China-Zhou et al
10 10 China- Zhang S
Taiwan
Japan-Ohsawa et al
8 8 Japan-Inoue et al
Japan Iguchi et al
6 6 Korea
Singapore-Chinese

4 4

2 2

0 0
<54 55-59 60-64 65-69 70-74 75-79 >80 <54 55-59 60-64 65-69 70-74 75-79 >80
Age (years) Age (Years)

Tse HF, et al. Heart Rhythm 2013

Incidence of AF in Device Population-
Insight from ASSET
East vs. West

Lau CP, ….Tse HF, et al JCE 2013

 Atrial Arrhythmias and Aging

Atrial Fibrillation Atrial Flutter

Wolf PA. Stroke. 1991 Granada et al. JACC 2000

 Projected Population with AF

Men Women
6000 4000
China
2050 USA
5000

Adults with Atrial Fibrillation, in thousands

Adults with Atrial Fibrillation, in thousands

2050
3000

4000

3000 2025 2000

2025
2050

2000 2050 2025

2025 1000
2000 2000
2000
1000 2000

0 0
60-64 60-69 60-74 60-79 60-85 60-64 60-69 60-74 60-79 60-85
Age, years Age, years

Tse HF, et al . Heart Rhythm 2013

 Ischemic Stroke and AF in China
Independent variables of stroke prevalence
!  29,079 pts from 14 population-
based cohorts across 13 provinces
in China in 2003
Prevalence of stroke in AF and non-AF cohorts

Zhou Z, & Hu D. J Epidemiol 2008;18:209–16.

Kaplan-Meier estimation of survival rates in patients with

! 2,683 consecutive patients with first- and without AF (Χ2 = 116.613, P < 0.001)
ever ischemic stroke enrolled from a
single center in China between 2002 1.0
and 2008
0.9
Survival rate

" 13.6% (n = 366) were diagnosed

with AF; 41.8% with VAF, 58.2% 0.8 2x ↑ No AF

AF
+No AF – censored
with NVAF +AF – censored
0.7
! Only 58.5% of AF pts had been
diagnosed prior to stroke onset 0.6
0 3 6 9 12
Lin S, et al. Cerebrovasc Dis 2011;31:419–26. Follow-up period (months)
 Do we need an additional
guidelines for Asia-Pacific region?
•  ? Ethnic differences on prevalence
of AF
•  ? Stroke risk related to AF in Asia-
pacific populations
•  ? Differences in the risk and benefit
of anticoagulation therapy for stroke
prevention
 Stroke risk Assessment with
CHA2DS2-VASc
CHA2DS2-VASc criteria Score CHA2DS2-VASc Rate of stroke/other TE
total score (%/year) (95% CI)*
Congestive heart failure/
1 0 0 (0–0)
left ventricular dysfunction
Hypertension 1 1 0.6 (0.0–3.4)
2 1.6 (0.3–4.7)
Age ≥75 yrs 2
3 3.9 (1.7–7.6)
Diabetes mellitus 1
4 1.9 (0.5–4.9)
Stroke/transient ischaemic 5 3.2 (0.7–9.0)
2
attack/TE
6 3.6 (0.4–12.3)
Vascular disease (prior
myocardial infarction, peripheral 1 7 8.0 (1.0–26.0)
artery disease or aortic plaque) 8 11.1 (0.3–48.3)
Age 65–74 yrs 1 9 100 (2.5–100)
Sex category (i.e. female *Theoretical rates without therapy corrected for the % of
1 patients receiving Aspirin within each group,
gender) assuming 22% reduction in risk
with Aspirin
TE = thromboembolism
Lip GYH et al. Chest 2010;137:263-72
 Estimation of Stroke Risk in Asian AF
Patients using CHADS2 & CHA2DS2-VASC

CHA2DS2-VASC score
5
CHADS2 score

2
? Lower risk of 1
AF-related stroke in Asia 0

Annual stroke rate (%)

Data from Lin LY, et al. Atherosclerosis 2011;217:292–295
 Estimation of Stroke Risk in Asian AF
Patients using CHADS2 & CHA2DS2-VASC

Ogawa S, ..Tse HF, et al. . Journal of Arrhythmia 2013

 Estimation of stroke risk in Chinese AF
Patients using CHADS2 & CHA2DS2-VASC
Percentage of patients with ischemic stroke-free survival (%)

No Aspirin/Warfarin

CHA2DS2-VASC: 0

CHA2DS2-VASC: 1

CHA2DS2-VASC: 2
CHA2DS2-VASC: 3
CHA2DS2-VASC: 5
CHA2DS2-VASC: 6
CHA2DS2-VASC: 4

Log-rank: 86.6, p<0.0001

Months

•  In Chinese patients with AF, CHA2DS2-VASC score predicts a high risk

of ischemic stroke vs Western population.
•  Warfarin therapy was much more effective than aspirin in reducing the
ischemic stroke risk.
•  The net clinical benefit favors warfarin therapy in Chinese patients with
AF in all combinations of stroke and ICH risk.
Siu CW, ….Tse HF. Heart Rhythm 2014
 Estimation of stroke risk in Chinese AF
Patients using CHADS2 & CHA2DS2-VASC
No#aspirin/warfarin#aspirin/
18 warfarin# N=9,727
Annual risk of ischemic stroke (%)

Warfarin#
16 13.18
12.69
14 11.58

12
9.56 9.53
10 8.74 8.86
7.84 8.04
8 6.64
6.79 6.34

6 5.08 5.19

3.86
4 2.41 3.11
3.63
2.07
2.01
2
0.50
0
0 1 2 3 4 5 6-9

CHA2DS2-VASC score
Siu CW, ….Tse HF. Heart Rhythm 2014
Estimation of stroke risk in Chinese AF Pts
in Taiwan using CHADS2 & CHA2DS2-VASC

Chao TF, et al. JACC 2014

Risk of Ischemic Stroke in AF Males in
Taiwan CHA2DS2-VASc = 1
Stratified by Component

Chao T-F, JACC 2015

 Age Cut-off for Estimation of Stroke Risk in
Chinese AF with CHA2DS2-VASC 0-1

#  For Taiwanese patients 50 to 64 years of age, the annual stroke risk was
1.78%, which may exceed the threshold for OAC use for stroke prevention.
#  Annual risk of ischemic stroke for AF patients <50 years of age was 0.53%,
which was truly low-risk, and OACs could be omitted.
Chao TF, et al. JACC 2015
Estimation of Stroke Risk in Japan using
CHADS2 & CHA2DS2-VASC

0.5%/yr

Suzuki S, et al. Cir J

Estimation of Stroke Risk in East vs West
using CHADS2 & CHA2DS2-VASC

? Study method
? Genetic
? Risk factors control

HKU AF CAL

Siu CW. JACC 2015

 Do we need an additional
guidelines for Asia-Pacific region?
•  ? Ethnic differences on prevalence
of AF
•  ? Stroke risk related to AF in Asia-
pacific populations
•  ? Differences in the risk and benefit
of anticoagulation therapy for stroke
prevention
Antithrombotic Therapy Based on
CHADS2 Score

Ogawa S, .. Tse HF, et al. Journal of Arrhythmia 2013

Antithrombotic Therapy Based on
CHADS2 Score

Ogawa S, .. Tse HF, et al. Journal of Arrhythmia 2013

Utilization of OAC in SPAF in Japan

Toyoda K, Cir J 2015

 Ethnic Difference:
Risk of Intracranial Hemorrhage with Warfarin for AF

1.0 80

Events / 1000 patient years

HR: 4.06, p<0.001

White 60
ICH-free probability

Cheung CM
2005
You JH
2005
Black 40

20

Hylek EM,
Asian 2003
0
<1.5 1.5 2.0 2.6 3.1 3.6 4.1 >4.5
INR
0.95 0 1 2 3 4 5 6 7 8 9 10
Years $ Risk of ICH in Chinese

1.1-1.2%/pt-yr in Chinese vs. 0.3-

Shen AY, et al. JACC 2007;50:309-15
0.6%/pt-yr
Target INR in Asian (J-
RHYTHM)
N=7406

Age >70
All

Inoue H, et al. Cir J 2014

Optimal INR Range for VKA Therapy
Based on Age

Ogawa S, .. Tse HF, et al. Journal of Arrhythmia 2013

 Net Clinical Benefit of Warfarin in Elderly
Chinese AF Patients (>80 yrs old)

Risk of ICH 0.9-1.3%

•  Chinese elderly patients with AF are at high risk of ischemic stroke.

•  Warfarin therapy reduces the ischemic stroke risk but with an increased
risk of ICH.
•  Nonetheless, net clinical benefit favors warfarin therapy in elderly
patients with AF in all combinations of stroke and ICH risk.

Siu CW, Tse HF. Cir EP 2014

 INR Control in RCT for AF
? Ethnic Difference

The higher risk of ischemic and hemorrhagic stroke in

Asian patients may be due to low average INR and
more difficult to achieve optimal TTR.

Chiang EC, et al Thromb Haemost 2014

 Selection of Stroke Prevention Therapies
for Non-valvular AF

TTR, %

Larsen TB & Lip GY. Lancet 2013 Apostolakis S, et al. Chest 2013
NOACs for SPAF
Asian vs Non-Asian

Sabir I, et al. Nat Rev Cardiol 2014

 ICH RE-LY

ROCKET AF

ARISTOTLE

ENGAGE AF

Yasaka M, Lip GY. Cir J 2014

 NOCA RCT:
Benefit of NOCA in Asian vs Non-Asian
Stroke and SEE Ischemic Stroke Hemorrhagic Stroke

Myocardial Infarction All cause mortality Intracranial Bleeding

Lip GY, et al. Int J Cardiol 2014

Real-World Experience of NOAC
in Chinese AF Patients

Ho CW, ……Tse HF, Siu CW. Stroke 2015

Real-World Experience of NOAC
in Chinese AF Patients

Ho CW, ……Tse HF, Siu CW. Stroke 2015

 APHRS Recommendations

Non-valvular AF

CHA2DS2-VASc score

0 1 ≥2

No antithromboitc Rx Dab/Api Dab/Api

W/Riv W/Riv

Ogawa S, Tse HF…... J Arrhythmia 2013

 Asia-Pacific HRS AF Survey
ESC APHRS

Baseline
AF Survey
AP office
Web-based
BMS/Pfizer
12 months
FU

Hong
Singapore Japan Taiwan Korea
Phase I Kong
(n=1000) (n=1000) (n=1000) (n=1000)
(n=1000)

Phase II
Other AP Regions

Sponsored by BMS/Pfizer
 Conclusions
!  In
Asian population, stroke risk can be predicted by
CHA2DS2-VASC, but is also higher in younger pts

!  OAC rather than antiplatelet should be use for SPAF

but is under-utilization and the optimal INR in Asian
remains unclear

!  NOACs are preferred in the Asian population due to

poor INR control and higher risk of intracranial
bleeding

!  Morestudies are needed to determine the optimal

approach for SPAF in Asia