1. Oral Rivaroxaban Compared with Subcutaneous Enoxaparin for Extended Thromboprophylaxis After Total Hip Arthroplasty: The RECORD1 Trial Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, Bandel TJ, Muehlhofer E, Misselwitz F Blood. 2007;110(11). Abstract #6.

2. Background: Thrombosis prophylaxis is recommended for at least 10 days, and for up to 4-5 weeks, after total hip arthroplasty (THA) Rivaroxaban is an oral, direct Factor Xa inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders Oral Rivaroxaban Compared with Subcutaneous Enoxaparin for Extended Thromboprophylaxis After Total Hip Arthroplasty: The RECORD1 Trial Eriksson B.I., et al. Blood. 2007;110(11):Abstract #6.

3. Objective: To determine the efficacy and safety of oral rivaroxaban, compared with subcutaneous enoxaparin, for 5 weeks of thrombosis prophylaxis in patients undergoing THA Oral Rivaroxaban Compared with Subcutaneous Enoxaparin for Extended Thromboprophylaxis After Total Hip Arthroplasty: The RECORD1 Trial Eriksson B.I., et al. Blood. 2007;110(11):Abstract #6.

4. Methods: Multinational, double-blind, double-dummy trial Inclusion criteria: –Patients ≥18 years, scheduled to undergo elective THR Major exclusion criteria: –Active bleeding or high risk of bleeding –Significant liver disease –Anticoagulant therapy that could not be stopped –Use of HIV-protease inhibitors Oral Rivaroxaban Compared with Subcutaneous Enoxaparin for Extended Thromboprophylaxis After Total Hip Arthroplasty: The RECORD1 Trial Eriksson B.I., et al. Blood. 2007;110(11):Abstract #6.

5. Study Design Rivaroxaban 10mg qd Start 6-8hr post-op Enoxaparin 40mg qd Begin evening before then restart 6-8hr post-op Mandatory, Bilateral Venography the day after treatment is completed 35±4 days Eriksson B.I., et al. Blood. 2007;110(11):Abstract #6.

6. Methods: Primary efficacy endpoint (composite): –Deep vein thrombosis (DVT) –Non-fatal pulmonary embolism (PE) –All-cause mortality Primary efficacy analysis: –A test for non-inferiority in the per-protocol (PP) population followed by a test for superiority in the modified intention-to-treat (mITT) population Oral Rivaroxaban Compared with Subcutaneous Enoxaparin for Extended Thromboprophylaxis After Total Hip Arthroplasty: The RECORD1 Trial Eriksson B.I., et al. Blood. 2007;110(11):Abstract #6.

7. Methods: The main secondary efficacy endpoint: –Major venous thromboembolism (VTE): the composite of proximal DVT, non-fatal PE and VTE-related death Primary Safety Endpoint: –Major bleeding during the active treatment period Secondary Safety Endpoint: –Non-major bleeding during the active treatment period Oral Rivaroxaban Compared with Subcutaneous Enoxaparin for Extended Thromboprophylaxis After Total Hip Arthroplasty: The RECORD1 Trial Eriksson B.I., et al. Blood. 2007;110(11):Abstract #6.

8. Results: A total of 4541 patients were randomized –4433 were eligible for the safety population –3153 for the mITT population –3029 for the PP population The criteria for non-inferiority were met and testing for superiority was performed Oral Rivaroxaban Compared with Subcutaneous Enoxaparin for Extended Thromboprophylaxis After Total Hip Arthroplasty: The RECORD1 Trial Eriksson B.I., et al. Blood. 2007;110(11):Abstract #6.

9. Results: Rivaroxaban significantly reduced the incidence of the primary efficacy endpoint (P<0.001) and major VTE (P<0.001), compared with enoxaparin, in the mITT population The incidence of major and non-major bleeding events was similar in both groups Oral Rivaroxaban Compared with Subcutaneous Enoxaparin for Extended Thromboprophylaxis After Total Hip Arthroplasty: The RECORD1 Trial Eriksson B.I., et al. Blood. 2007;110(11):Abstract #6.

10. Results Rivaroxaban 10 mg od % (n/N) Enoxaparin 40 mg od % (n/N) Relative risk reduction % (95% CI) P-value for difference DVT, non-fatal PE, and all-cause mortality 1.1% (18/1595) 3.7% (58/1558) 70% (49-82%) P<0.001 Major VTE 0.2% (4/1686) 2.0% (33/1678) 88% (66-96%) P<0.001 Major bleeding 0.3% (6/2209) 0.1% (2/2224) --P=0.178 Non-major bleeding 5.8% (128/2209) 5.8% (129/2224) --P=1.000 Eriksson B.I., et al. Blood. 2007;110(11):Abstract #6.

11. 6 Incidence (%) 0 1 2 3 4 5 Rivaroxaban 10 mg once daily 18/1595 Enoxaparin 40 mg once daily 58/1558 3.7% 1.1% RRR* = 70% ARD † = –2.6% (–3.7, –1.5) p<0.001 *Relative risk reduction based on raw incidences; † absolute weighted risk difference (with 95% CI); mITT population, n=3153 Total VTE Primary Efficacy Endpoints Eriksson B.I., et al. Blood. 2007;110(11):Abstract #6.

12. Incidence (%) 0 1 2 3 4 Rivaroxaban 10 mg once daily 6/2193 Enoxaparin 40 mg once daily 11/2206 ARD † = –0.2% (–0.6, 0.1) p=0.222 0.3% 0.5% Incidence (%) 0 1 2 3 4 Rivaroxaban 10 mg once daily 4/1686 Enoxaparin 40 mg once daily 33/1678 RRR* = 88% ARD † = –1.7% (–2.5,–1.0 ) p<0.001 2.0% 0.2% Major VTE Symptomatic VTE in safety population mITT population valid for major VTE, n=3364; safety population who underwent surgery, n=4399; *relative risk reduction based on raw incidences; † absolute weighted risk difference (with 95% CI) Primary Efficacy Endpoints Cont. Eriksson B.I., et al. Blood. 2007;110(11):Abstract #6.

13. 0% Rivaroxaban better Enoxaparin better Absolute difference between rivaroxaban and enoxaparin (delta) Sample size determination: Estimated incidence of primary efficacy endpoint with both drugs: 8% Type 1 error rate of 2.5% Estimated venographic invalidity rate: 25% Test 1. Rivaroxaban non-inferior Test 2. Rivaroxaban superior 0%+3.5% Statistical Analysis of the Primary Efficacy Endpoints Eriksson B.I., et al. Blood. 2007;110(11):Abstract #6.

14. On-treatment major bleeding; *unweighted absolute risk difference (with 95% CI); safety population, n=4433 Major bleeding 4 0 1 2 3 p=0.178 ARD* = 0.18% (–0.1, 0.5) 0.09% 0.27% Rivaroxaban 10 mg once daily 6/2209 Enoxaparin 40 mg once daily 2/2224 Incidence (%) Safety Endpoints Eriksson B.I., et al. Blood. 2007;110(11):Abstract #6.

15. Conclusions: Rivaroxaban was significantly more effective than enoxaparin for extended prophylaxis after THA, with a similar safety profile This is the first pivotal trial to demonstrate the efficacy and safety of a fixed, unmonitored dose of an oral, direct Factor Xa inhibitor – rivaroxaban – for extended thromboprophylaxis after THA Oral Rivaroxaban Compared with Subcutaneous Enoxaparin for Extended Thromboprophylaxis After Total Hip Arthroplasty: The RECORD1 Trial Eriksson B.I., et al. Blood. 2007;110(11):Abstract #6.