1. Efficacy and Safety of Dabigatran vs
Efficacy and Safety of Dabigatran vs. Warfarin in Patients with Atrial Fibrillation - Japanese population in the RE-LY ® -
Shinya Goto , MD., PhD. Tokai University School of Medicine C. Michael Gibson, M.S., M.D. Beth Israel Deaconess Medical Center, Harvard Medical School, Duke Clinical Research Institute

2. RE-LY® - Overall Summary
Dabigatran etexilate has been shown to concurrently reduce both thrombotic and haemorrhagic events
Both doses of dabigatran provide different and complementary advantages over warfarin
150 mg BID showed 35% statistically significant reduction in stroke/systemic embolism with similar bleeding
110 mg BID showed comparable rates of stroke/systemic embolism has significantly less bleedings with similar efficacy

3. RE-LY® - Baseline Characteristics in Japanese Subjects
Overall
Japan
Randomized
18,113
326
Mean age (years)
71.5
71.2
Male (%)
63.6
76.7
CHADS2 score
(mean)
0-1 (%)
(%)
3+ (%)
2.1
31.9
35.6
32.5
2.2
31.3
34.0
34.7
Prior stroke / SEE / TIA(%)
21.8
33.1
Prior MI (%)
16.6
5.5
CHF (%)
32.0
31.0
Baseline ASA (%)
39.8
35.9
VKA naive (%)
50.4
56.1
Over all : calculated from NEJM, 2009, 361, 12
Hori M, et al: Circ J 2011; 75: , 2011

4. RE-LY® - Stroke or Systemic Embolism
Overall
Japan
% per year
150mg bid mg bid
(n=134/6,076) (n=183/6,015) (n=202/6,022)
% per year
150mg bid mg bid
(n=1/111) (n=12/107) (n=4/108)
RR 0.65 (95% CI: )
RR 0.25
RR 0.90
(95% CI: )
RR 0.52
Connolly SJ, et al.: N Engl J Med 363, , 2010
Hori M, et al: Circ J 2011; 75: , 2011

5. RE-LY® - Plasma Concentration of Dabigatran in Overall and Japanese
Overall Japanese
Overall Japanese
Cpre,ss: Pre dose plasma concentrations at steady state
C2,ss : Plasma concentration at 2 hours after drug administration at steady state (approximate maximum plasma concentration)
Hori M, et al: Circ J 2011; 75: , 2011

6. Country Distribution of Mean Time in Therapeutic Range (TTR) in the RE-LY®
Wallentin L, et al.: Lancet, 376: , 2010

7. RE-LY® - INR Control / Time racio
Region N
INR <2
INR 2-3
INR>3
Overall
5,789
22.2%
64.4%
13.5%
Japan
108
36.8%
57.6%
5.6%
JCS guideline for pharmacotherapy of atrial fibrillation2008:
2.0~3.0 for <70 years
1.6~2.6 for ≧70 years
Over all : calculated from NEJM, 2009, 361, 12

8. RE-LY® - Japanese Population Conclusions
The result of Japanese subgroup is basically consistent with overall results of RE-LY®.
The demographics of the Japanese subgroup differ from the overall population in prior stroke and MI of RE-LY but the overall risk score is similar.
PK profile between Japanese subgroup and overall is similar.
Based on the Japanese guideline criteria, the INR control of warfarin was well-controlled.