ARIXTRA fondaparinux sodium in the prevention of venous

ARIXTRA® (fondaparinux sodium) in the prevention of venous thromboembolism after hip replacement surgery KA Bauer, BI Eriksson, MR Lassen, and AGG Turpie on behalf of the Steering Committees of the Pentasaccharide Orthopaedic Prophylaxis Studies SANOFI-SYNTHELABO ARIXTRA® 1

EPHESUS AND PENTATHLON 2000: OBJECTIVE AND DESIGN u To compare the efficacy and safety of o. d. s. c. injections of Arixtra® 2. 5 mg with enoxaparin in preventing venous thromboembolism (VTE) in patients undergoing elective hip replacement surgery. u Two multicenter, randomized, double-blind, two-parallel-group comparative trials in 4584 patients. SANOFI-SYNTHELABO ARIXTRA 2

EPHESUS AND PENTATHLON 2000: DESIGN Treatment 7 ± 2 Days start 6 ± 2 hrs post-op Arixtra® 2. 5 mg o. d. R Enoxaparin 40 mg o. d. or 30 mg b. i. d. start pre-op or post-op Venogram Day 5– 11 SANOFI-SYNTHELABO ARIXTRA Follow up Day 42 ± 7 3

EPHESUS AND PENTATHLON 2000: ENDPOINTS u Primary efficacy: VTE up to day 11 u deep-vein thrombosis (DVT) detected by mandatory bilateral venography, or u documented symptomatic DVT, or u pulmonary embolism. u Primary safety: Major bleeding. SANOFI-SYNTHELABO ARIXTRA® 4

EPHESUS AND PENTATHLON 2000: EFFICACY RESULTS 10 VTE (%) 8 p =1. RR 43. 0%1 2 0 8. 8% u Compared with enoxaparin Arixtra® also reduced the incidence of: n=151 6 4 u 3411 (74. 4%) patients included in the primary efficacy analysis 4 x 10 -5 5. 0% u any DVT from 8. 6% to 4. 7% u any proximal DVT from 1. 9% to 1. 2% u distal-only DVT from 7. 0% to 3. 8% n=85 Arixtra® n = 1, 695 Enoxaparin n = 1, 716 1. Turpie et al. Arch Intern Med 2002 SANOFI-SYNTHELABO ARIXTRA 5

EPHESUS AND PENTATHLON 2000: SAFETY RESULTS Arixtra® Enoxaparin N=2, 268 n (%) N=2, 262 n (%) Fatal bleeding 0 0 Bleeding in critical organ 0 0 Bleeding leading to reoperation 7 (0. 3) 5 (0. 2) Bleeding with a bleeding index* 2 60 (2. 6) 37 (1. 6) *The bleeding index was calculated as follows: [number of units of packed red blood cells or whole blood transfused] + [(pre-bleeding) - (post-bleeding) hemoglobin (g/dl) values]. SANOFI-SYNTHELABO ARIXTRA® 6

EPHESUS AND PENTATHLON 2000: CONCLUSION In patients undergoing elective hip replacement surgery, Arixtra® provided a major benefit over enoxaparin in preventing VTE without increasing the risk of clinically relevant bleeding SANOFI-SYNTHELABO ARIXTRA® 7