1. Manesh R. Patel, M.D., Kenneth W. Mahaffey, M.D., Jyotsna Garg, M.S., Guohua Pan, Ph.D., Daniel E. Singer, M.D., Werner Hacke, M.D., Ph.D., Gunter Breithardt, M.D., Jonathan L. Halperin, M.D., Graeme J. Hankey, M.D., Jonathan P. Piccini, M.D., Richard C. Becker, M.D., Christopher C. Nessel, M.D., John F. Paolini, M.D., Ph.D., Scott D. Berkowitz, M.D., Keith A.A. Fox, M.B., Ch.B., Robert M. Califf, M.D., and the ROCKET AF Steering Committee, for the ROCKET AF Investigators* N Engl J Med 365;10, September 8, 2011 R3. A-ri Shin / Prof. Won Kim Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation Journal conference 2011.09.21

2. Atrial fibrillation is associated with an increase in the risk of ischemic stroke For stroke prevention in patients with atrial fibrillation - Warfarin, vitamin K antagonists highly effective and recommended for persons at increased risk but, food and drug interactions necessitate frequent coagulation monitoring and dose adjustments - Rivaroxaban, oral factor Xa inhibitor provide more consistent and predictable anticoagulation than warfarin Background

3. Purpose In patients with nonvalvular atrial fibrillation who were at moderate-to-high risk for stroke Once-daily oral Rivaroxaban Dose-adjusted Warfarin VS Prevention of stroke and systemic embolism ? Evaluation of bleeding events rate ?

4. Study Design and Participants - ROCKET AF : The Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation - Multicenter, randomized, double-blind trial - From December 18, 2006, through June 17, 2009 - Recruited patients with nonvalvular atrial fibrillatioin, as documented on echocardiography, who were at moderate-to-high risk for stroke. c.f) Indication of Elevated risk 1) history of stroke 2) history of transient ischemic attack 3) history of systemic embolism 4) at least two of the following risk factors : Heart failure, LVEF 75 yrs Total 14,264 patients were enrolled Methods

5. Study Treatment - Randomly assigned to receive fixed dose rivaroxaban (20 mg daily) or adjusted-dose warfarin (target INR : 2~3) Outcomes - Primary efficacy end point : composite of stroke (ischemic or hemorrhagic) and systemic embolism - Secondary efficacy end points : composite of stroke, systemic embolism, death from cardiovascular causes or myocardial infarction - Principal safety end point : composite of major and nonmajor clinically relevant bleeding events Methods

6. Results 1)Patient Characteristics and Treatments 2)Primary End Points 3)Bleeding Outcomes

7. 1. Patient Characteristics and Treatments

8. 2. Primary Outcomes – (1)

9. 3. Primary Outcomes – (2)

10. 3. Primary Outcomes – (3)

11. 3. Bleeding Outcomes

12. In patients with atrial fibrillation 1) Rivaroxaban was noninferior to Warfarin for the prevention of subsequent stroke or systemic embolism. 2) No significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the Rivaroxaban group. Conclusion