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

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

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 (%) 2 (%) 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: 800 - 805, 2011

RE-LY® - Stroke or Systemic Embolism Overall Japan % per year 150mg bid 110mg bid (n=134/6,076) (n=183/6,015) (n=202/6,022) % per year 150mg bid 110mg bid (n=1/111) (n=12/107) (n=4/108) RR 0.65 (95% CI: 0.52-0.81) RR 0.25 RR 0.90 (95% CI: 0.74-1.10) RR 0.52 Connolly SJ, et al.: N Engl J Med 363, 1875-1876, 2010 Hori M, et al: Circ J 2011; 75: 800 - 805, 2011

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: 800 - 805, 2011

Country Distribution of Mean Time in Therapeutic Range (TTR) in the RE-LY® Wallentin L, et al.: Lancet, 376: 975-83, 2010

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

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.