Department of Cardiology, Hirosaki University Graduate School of Medicine, Japan

Professor, Ken Okumura

Update in ESC: Dabigatran among OACUpdate in ESC: Dabigatran among OAC

Age 81 Female (Living alone, ADL: independent )Chronic AF 　 HT(-), No heart disease, DM(-), LAD 43mm

Age 81 Female (Living alone, ADL: independent )Chronic AF 　 HT(-), No heart disease, DM(-), LAD 43mm

2004Jan Feb Mar Apr May Oct Nov Dec

2005Jan Feb Mar Apr

2.5mg 1.5mg 2.5mg2.5mg

Warfarin (2002~)

nose bleed dementia Strokedementia

2.16

1.541.36

2.1 2.15

0.91

2.13

3.53

1.35

0.78 0.81 0.87

1.16

0.81

0

1

2

3

4

PT

-IN

R

dementia

aspirin

29th 4,2005 14th 5,2005

Age 81 Female (Living alone, ADL: independent )Chronic AF 　 HT(-), No heart disease, DM(-), LAD 43mm

Age 81 Female (Living alone, ADL: independent )Chronic AF 　 HT(-), No heart disease, DM(-), LAD 43mm

n=768 (Oct, 2005~Jan, 2008)m-Rankin scale

31% 54%

Lacunar(n=215)

Atherothrombotic infarction

(n=308)

Cerebral embolism

(n=245)

Ken Okumura, Norihumi Metoki, Jyoji Hagii 　 Japanese Journal of Electrocardiology 2011;31:292-296

mRS by subtype of brain infaction (HIROSAKI Stroke and Rehabilitation Center)

mRS by subtype of brain infaction (HIROSAKI Stroke and Rehabilitation Center)

0 20 40 60 80 100(%)

0

1

2

3

4

5

6

No symptoms

Dead

Bedridden

Able to carry out all usual activities

Able to look after own affairs without assistance

Requires some help, but able to walk unassisted

Unable to walk unassisted

ECG on admission

Ken Okumura, Norihumi Metoki, Jyoji Hagii 　 Japanese Journal of Electrocardiology 2011;31:292-296

Prevalence of AF among Cerebral embolism patients:267 consecutive patients during 2008-2009

(HIROSAKI Stroke and Rehabilitation Center)

Prevalence of AF among Cerebral embolism patients:267 consecutive patients during 2008-2009

(HIROSAKI Stroke and Rehabilitation Center)

AF(-)n=128(48%)

AF(+)n=139(52%)

Sustained AFn=120(45%)paroxysmal

AFn=80(30%)

AF(-)n=67(25%)

Data from previous Dr & ECG during hospitalization

Sustained(n=120)

Paroxysmal(n=80)

Not defined AF

(n=67)

Percentage of patients with internal carotid artery stenosis

(P ＝ NS)

Percentage of patients withmRS = 4,5,6

(P ＝ NS)

*Patients with acute stroke within 3 hours of onset were treated with tPA

Severity of stroke by AF typeSustained AF vs Paroxysmal AF vs Not defined AF

(HIROSAKI Stroke and Rehabilitation Center)

Severity of stroke by AF typeSustained AF vs Paroxysmal AF vs Not defined AF

(HIROSAKI Stroke and Rehabilitation Center)

0 20 40 60 80 100(%)

23 97

12 68

9 58

0 20 40 60 80 100(%)

57 63

33 47

25 42

CHADS2 Score and Severity of strokeCHADS2=0,1 Score (n=41) vs CHADS2=2-6 Score (n=159)

(HIROSAKI Stroke and Rehabilitation Center)

CHADS2 Score and Severity of strokeCHADS2=0,1 Score (n=41) vs CHADS2=2-6 Score (n=159)

(HIROSAKI Stroke and Rehabilitation Center)

0 20 40 60 80 100(%)

9 32

34 125

0 20 40 60 80 100(%)

17 24

73 86

CHADS2=0,1(n=41)

CHADS2=2-6(n=159)

Percentage of patients with internal carotid artery stenosis

(P ＝ NS)

Percentage of patients withmRS = 4,5,6

(P ＝ NS)

CHADS2 Score

(%)

1.9% 2.8% 4.0%5.9%

8.5%

12.5%

18.2%Incidence for stroke

National Registry of AF

20

40

60

80

100

0

(cases)

The Japanese Society of Electrocardiology J-RHYTHM Registry

CHADS2 Score of registered AF patients (n=7,937)

The Japanese Society of Electrocardiology J-RHYTHM Registry

CHADS2 Score of registered AF patients (n=7,937)

35

30

25

20

15

10

5

00 1 2 3 4 5 6

-1 -0.5 0 0.5 1 1.5 2 2.5 3 3.5

4-6

3

2

1

0

CH

AD

S2 s

core

2.220.58 3.75

2.071.21 2.79

0.970.43 1.41

0.19-0.27 0.45

-0.11-0.44 0.20

Net Clinical Benefit in ATRIA Study(Singer DE, et al. Ann Intern Med 2009;151:297-305)

Net Clinical Benefit in ATRIA Study(Singer DE, et al. Ann Intern Med 2009;151:297-305)

13,559 adults with non-valvular atrial fibrillation at Kaiser Permanente Northern California(73 years median age; Male 57%; more than 66,000 person-years

of observation; 53% of patients were receiving warfarin treatment.)

→ 1,092 thromboembolic events, 299 intracranial hemorrhagic events

Net clinical benefit of warfarin = 0.68%/yr

Net clinical benefit of patients with Prior Stroke = 2.48%/yr

Net Clinical Benefit ＝ (TE rate off warfarin −TE rate on warfarin) − 1.5 x (ICH rate on warfarin −ICH rateoff warfarin)

Worse with Warfarin Better with Warfarin

Intracranial hemorrhage rateIntracranial hemorrhage rate

Connolly SJ, et al: N Engl J Med 361, 1139-1151, 2009Connolly SJ, et al: N Engl J Med 363, 1875-1876, 2010

Intracranial hemorrhage: Hemorrhagic Stroke (Intracerebral hemorrhage), Subdural hematoma and Subarachnoid hemorrhage

0.4

0.6

0.8

1.0

0.2

Dabigatran110mg bid(n=27/6,015)

Warfarin

(n=90/6,022)

0

0.760.76

0.230.23

RRR70%

Dabigatran150mg bid(n=38/6,076)

0.320.32

RR 0.41 (95% CI: 0.28–0.60)P<0.001

RR 0.30 (95% CI: 0.19–0.45)P<0.001

RRR59%

Eve

nt r

ate

(% p

er

year

)

Urgent Statement on Antithrombotic Therapy ofAtrial Fibrillation : JCS Guideline Statement (Aug.2011)

Urgent Statement on Antithrombotic Therapy ofAtrial Fibrillation : JCS Guideline Statement (Aug.2011)

JCS: Urgent Statement 2011 　 http://www.j-circ.or.jp/guideline/pdf/statement.pdf

CHADS2 Score

Heart failure 1point Hypertension 1point ≥75 years old 1point Diabetes 1point History of cerebral infarction or TIA2points

Mitral stenosisor

mechanical valve

1point≥2points

Other risk factors

　 Cardiomyopathy　 65 to 74 years old　 Female patients　 Coronary heart disease　 Thyrotoxicosis

Non-valvular AF

WarfarinINR2.0~3.0

Recommended

WarfarinINR2.0 to 3.0 for < 70 years oldINR1.6 to 2.6 for ≥ 70 years old

Recommended

Dabigatran

WarfarinINR2.0 to 3.0 for < 70 years oldINR1.6 to 2.6 for ≥ 70 years old

Considered

Dabigatran

WarfarinINR2.0 to 3.0 for < 70 years oldINR1.6 to 2.6 for ≥ 70 years old

Considered

Dabigatran

Recommended