RECORD studies in total knee replacement
The RECORD3 and RECORD4 studies showed that oral rivaroxaban offered significantly superior efficacy compared with subcutaneous enoxaparin for the prevention of the primary efficacy endpoint (composite of any deep vein thrombosis [DVT], non-fatal pulmonary embolism [PE] and all-cause mortality), with a similar safety profile in adult patients after total knee replacement (TKR) surgery. Prophylaxis was administered for 10±4 days in both studies.4, 69
The American college of Chest Physicians (ACCP) guidelines recommend that patients undergoing TKR receive thromboprophylaxis for at least 10 days.6
RECORD3: Rivaroxaban versus enoxaparin in TKR
RECORD3 (N=2531) met its primary efficacy endpoint and showed that oral rivaroxaban (10 mg tablet od) offered significantly superior efficacy, with a similar safety profile to enoxaparin (40 mg od) for 12±2 days in adult patients.4
Rivaroxaban demonstrated:
- Significantly superior efficacy for the primary endpoint (total VTE)
- Significantly lower rates of major and symptomatic venous thromboembolic events
- A similar safety profile to enoxaparin
Primary efficacy endpoint
Thromboprophylaxis for 12±2 days with rivaroxaban resulted in a significantly greater reduction in the primary efficacy endpoint, total VTE compared with enoxaparin: relative risk reduction 49%
Secondary efficacy endpoints
Rivaroxaban significantly reduced the relative risk of major VTE (proximal DVT, PE and VTE-related death) by 62% and symptomatic VTE by 66% compared with enoxaparin.
Note: This is the first time since the introduction of unfractionated heparin that prophylaxis with an anticoagulant has led to a significant reduction in symptomatic venous thromboembolic events after major orthopaedic surgery on the lower limb.
Reassuring safety
The rates of major bleeding were low and not statistically different between the rivaroxaban and enoxaparin groups.
Adverse events
The overall incidence of adverse events, including serious drug-related adverse events, was similar with rivaroxaban and enoxaparin.
RECORD4: Rivaroxaban versus enoxaparin in TKR
RECORD4 (N=3148) met its primary efficacy endpoint and showed that oral rivaroxaban (10 mg tablet od) offered superior efficacy, with a similar safety profile to subcutaneous enoxaparin (30 mg twice daily) for 12±2 days in adult patients.
Rivaroxaban demonstrated:
- Significantly superior efficacy for the primary endpoint (total VTE)
- Low rates of major and symptomatic venous thromboembolic events
- A similar safety profile to enoxaparin
Primary efficacy endpoint
Thromboprophylaxis for 12±2 days with rivaroxaban resulted in a significantly greater reduction in the primary efficacy endpoint, total VTE, compared with enoxaparin: relative risk reduction 31%.
Secondary efficacy endpoints
Incidence rates of major VTE and symptomatic VTE were lower with rivaroxaban compared with enoxaparin but were not significantly different between groups.
Reassuring safety
The rates of major bleeding were low and not statistically different between the rivaroxaban and enoxaparin groups.
Adverse events
The overall incidence of AEs, including serious drug-related AEs, was similar with rivaroxaban and enoxaparin.
RECORD1–3 pooled analysis: Rivaroxaban versus enoxaparin
The RECORD1, 2, and 3 studies compared oral rivaroxaban 10 mg od – initiated postoperatively – with subcutaneous enoxaparin od started preoperatively for the prevention of VTE in 9581 adult patients undergoing elective hip or knee replacement surgery.2, 3, 4
A pooled analysis of the data from RECORD1, 2 and 3 investigated whether rivaroxaban was more effective than enoxaparin in reducing the incidence of symptomatic venous thromboembolism (VTE) and all-cause mortality.67
Rivaroxaban demonstrated:
Rivaroxaban demonstrated:
- Significant reduction of symptomatic VTE and all-cause mortality
- A similar overall safety profile to enoxaparin
Background
The results of the individual studies in the RECORD programme demonstrated that oral rivaroxaban (10 mg od) was significantly more effective than subcutaneous enoxaparin (40 mg od) for the prevention of VTE following hip (RECORD1) or knee (RECORD3) replacement surgery with similar rates of bleeding. RECORD2 demonstrated the benefit of extended thromboprophylaxis with rivaroxaban after hip replacement surgery.
Outcome measures
The primary efficacy outcome was the composite of symptomatic VTE (symptomatic DVT and symptomatic non-fatal PE and all-cause mortality at 2 weeks.
The secondary efficacy outcome was the composite of symptomatic VTE and all-cause mortality at the end of the planned medication period, which includes the placebo-controlled period in RECORD2.
The primary safety outcomes were the incidence of major bleeding during the active and total treatment periods. Other safety outcomes included any on-treatment bleeding up to 2 days after the last intake of study medication, excessive wound haematoma, surgical-site bleeding, AEs and all-cause-mortality over the entire study period.
Efficacy outcomes
Rivaroxaban was significantly more effective than enoxaparin in reducing the incidence of symptomatic VTE and all-cause mortality.
An early and sustained reduction in the incidence of symptomatic VTE and all-cause mortality in favour of rivaroxaban was seen, with differences persisting after the end of the studies.
Reassuring safety
The incidence of major bleeding was similar for the rivaroxaban and enoxaparin regimens, even with RECORD2 comparing 5 weeks of rivaroxaban with 2 weeks of enoxaparin.
The incidence of other adverse events was similar between groups.
The cardiovascular safety profile of both drugs was similar.
- 4 - Lassen MR, Ageno W, Borris LC, et al; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008;358(26):2776-2786.
- 69 - Turpie AGG, Lassen MR, Davidson BL, et al; RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009;373(9676):1673-1680
- 6 - Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 suppl):381S-453S.
- 2 - Eriksson BI, Borris LC, Friedman RJ, et al; RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008;358(26):2765-2775.
- 3 - Kakkar AK, Brenner B, Dahl OE, et al; RECORD2 Investigators. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet. 2008;372(9632):31-39.
- 67 - Eriksson BI, Kakkar AK, Turpie AGG, Lassen MR, et al. Oral rivaroxaban for the prevention of symptomatic venous thromboembolism after elective hip and knee replacement. J Bone Joint Surgery. 2009;91-B:636-644.
- Efficacy
- The ability of a drug to produce the desired effect.
- Subcutaneous
- Introduced beneath the skin.
- Thrombosis
- Formation of a clot inside a blood vessel.
- Thromboprophylaxis
- Preventative treatment for blood clotting.
- Relative Risk Reduction
- Proportion of the control group experiencing a given outcome minus the proportion of the treatment group experiencing the outcome, divided by the proportion of the control group experiencing the outcome.
- Venous thromboembolism
- A disease process beginning with a blood clot occurring within the venous system, including deep vein thrombosis and pulmonary embolism.
- Deep vein thrombosis
- A blood clot in a deep vein, usually resulting from damage to the vein or blood flow slowing down or stopping. Usually DVTs are found in the leg, but can also be in the arm. Distal DVTs are found in deep veins of the calf, and are the most common type of DVT. Proximal DVTs are found in the legs above the calf muscle up to the waist.
- Pulmonary embolism
- A potentially fatal condition caused by a blood clot blocking a vessel in the lung: usually the clot originates from a DVT in the legs. PE can result in permanent lung damage.
- Major orthopaedic surgery
- Major operations on the bones or joints including total hip or knee replacement surgery.
