1. H.R. Buller, G. Agnelli Presented at the XXIst Congress of International Society on Thrombosis and Haemostasis (ISTH) 2007 Meeting, July 6-12th in Geneva, Switzerland. Treatment of Proximal Deep Vein Thrombosis (DVT): Rivaroxaban Once or Twice Daily Had Similar Efficacy and Safety to Standard Therapy in Phase II Studies

2. Background: Rivaroxaban is an oral, direct Factor Xa inhibitor Objective: To determine the safety and efficacy of –Once or twice daily dosing of Rivaroxaban –In patients with acute, systomatic, proximal DVT without pulmonary embolism (PE) –Relative to standard therapy heparin/LMWH+vitamin K antagonist [INR 2–3] Treatment of Proximal DVT Buller, H.R. and G. Agnelli. Presented at ISTH 2007 in Geneva, Switzerland, abstract #O-W-052.

3. Methods: EINSTEIN-DVT (n=543) Patients received: –Rivaroxaban 20 mg once daily (od) –Rivaroxaban 30 mg od –Rivaroxaban 40 mg od –Or standard therapy Efficacy outcome: –Symptomatic, recurrent DVT or symptomatic PE recurrent venous thromboembolism [VTE] –And asymptomatic deterioration on ultrasonography (US) or perfusion lung scan, at 3 months Treatment of Proximal DVT Buller, H.R. and G. Agnelli. Presented at ISTH 2007 in Geneva, Switzerland, abstract #O-W-052.

4. Methods: ODIXa-DVT (n=613) Patients received: –Rivaroxaban 10 mg twice daily (bid) –Rivaroxaban 20 mg bid –Rivaroxaban 30 mg bid –Or standard therapy Efficacy outcome: –Thrombus regression on ultrasonography without recurrent VTE at 3 weeks –Recurrent VTE and asymptomatic deterioration on ultrasonography at 3 months Treatment of Proximal DVT Buller, H.R. and G. Agnelli. Presented at ISTH 2007 in Geneva, Switzerland, abstract #O-W-052.

5. Eligible patients: those with symptomatic, proximal DVT at baseline Enoxaparin (1 mg/kg) *Number of patients randomized; CCUS: complete compression ultrasound; PLS: perfusion lung scan; CUS: compression ultrasound Study Designs Buller, H.R. and G. Agnelli. Presented at ISTH 2007 in Geneva, Switzerland, abstract #O-W-052.

6. Results 20 mg30 mg40 mg60 mg Standard Therapy ODIXa-DVT (bid study) Efficacy outcome (%)1.1--1.1/3.0*1.0 Major bleeding (%)1.7--1.7/1.7*3.00 EINSTEIN-DVT (od study) Efficacy outcome (%)6.15.46.6--9.9 Major bleeding (%)0.71.50--1.5 *Results are shown as 20 mg bid/40 mg bid. Table: Rivaroxaban (total daily dose) Efficacy Outcome at 3 Months 20mg bid40mg bid60mg bid40mg od Standard Therapy Thrombus regression 53.0%59.2%43.8%45.9% Thrombus Regression at 3 Weeks Buller, H.R. and G. Agnelli. Presented at ISTH 2007 in Geneva, Switzerland, abstract #O-W-052.

7. Conclusion: Rivaroxaban given either once or twice daily had similar efficacy and safety to standard therapy –In patients with acute, systematic, proximal DVT without pulmonary embolism (PE) This oral direct factor Xa inhibitor can be given as the sole treatment in a fixed dose appears to be a very attractive alternative to standard therapy in patients with DVT Treatment of Proximal DVT Buller, H.R. and G. Agnelli. Presented at ISTH 2007 in Geneva, Switzerland, abstract #O-W-052.