Abstract
Background Thromboprophylaxis for at least 10 days and for up to 4–5 weeks is recommended 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. RECORD1 was a phase III, multinational, randomized, double-blind, double-dummy trial, conducted to determine the efficacy and safety of oral rivaroxaban, compared with subcutaneous enoxaparin, for 5 weeks of thromboprophylaxis in patients undergoing THA.
Methods Patients received rivaroxaban 10 mg beginning 6–8 hours after surgery and once daily (od) thereafter, or enoxaparin 40 mg od, beginning the evening before surgery (restarting 6–8 hours after surgery). Therapy continued for 35±4 days and mandatory, bilateral venography was conducted the next day. The primary efficacy endpoint was the composite of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE), and all-cause mortality. The primary efficacy analysis was 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. The main secondary efficacy endpoint was major venous thromboembolism (VTE): the composite of proximal DVT, non-fatal PE and VTE-related death. Major and non-major bleeding during the active treatment period were the primary and secondary safety endpoints, respectively.
Results A total of 4541 patients were randomized; 4433 were eligible for the safety population, 3153 for the mITT population, and 3029 for the PP population. The criteria for non-inferiority were met and testing for superiority was performed. 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 (Table). The incidence of major and non-major bleeding events was similar in both groups (Table). 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.
| . | Rivaroxaban 10mg 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 |
| . | Rivaroxaban 10mg 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 |
Author notes
Disclosure: Employment: Tiemo Bandel, Eva Muehlhofer, Frank Misslewitz: Bayer HealthCare. Consultancy: All authors: Bayer HealthCare; Richard Friedman: Boehringer Ingleheim and sanofi-aventis; Sylvia Haas: Bristol-Myers Squibb. Ownership Interests:; Eva Muehlhofer: Bayer HealthCare. Research Funding: All authors: Bayer HealthCare; William Geerts: sanofi-aventis; Sylvia Haas: sanofi-aventis. Honoraria Information: William Geerts: Bayer HealthCare, Pfizer, sanofi-aventis. Membership Information: William Geerts: GlaxoSmithKline, Pfizer, sanofi-aventis. Off Label Use: Rivaroxaban is in an advanced stage of development, but not yet licensed.
