Results from a pre-specified pooled analysis of the four, double-blind, double-dummy phase 3 (RECORD) studies have been presented as a conference abstract at the 50th Meeting of the American Society of Hematology (ASH). Rivaroxaban was shown to be superior to enoxaparin regimens in reducing the composite clinical outcome of symptomatic VTE and death, with no significantly increased risk of major bleeding in patients undergoing major orthopaedic surgery.
Rivaroxaban was marketed in October 2008 for the primary prevention of venous thromboembolic events in adults who have undergone either elective total hip or knee replacement, and it is a similar price to dabigatran▼. NICE has already recommended the latter as an option for use in patients undergoing orthopaedic surgery, and guidance on rivaroxaban is anticipated in June 2009. Local decision making bodies will need to consider the role of both drugs and plan for the implementation of NICE guidance.
What is the background to this?
Over 12,500 people undergoing orthopaedic (knee or hip replacement) surgery were involved in these studies, the primary efficacy outcome of which was a composite of any deep vein thrombosis(DVT), non-fatal pulmonary embolism (PE), or death from any cause. Patients were randomised to receive oral rivaroxaban 10mg once daily (o.d.) starting 6 to 8 hours after surgery or subcutaneous enoxaparin either 40mg twice daily (b.d.) the evening before surgery (RECORD 1–3) or 30mg b.d. 12–24 hours after wound closure or adequate haemostasis ( RECORD 4, US regimen only). Further information on the individual, published RECORD studies can be found in a previous blog.
What does this study claim?
This pre-specified pooled analysis evaluated the effect of rivaroxaban on a primary efficacy composite outcome of symptomatic venous thromboembolism (VTE) (comprising DVT or PE) and all-cause mortality, and on bleeding. All outcomes were analysed in two time windows:
- The head-to-head treatment pool, i.e. the enoxaparin-controlled period common to all studies of12 days (+/- 2 days) post surgery
- The total study duration pool i.e. planned treatment period and 30–35 days follow-up.
The full details of the methodology used to pool data are not recorded in the abstract.
The incidence of symptomatic VTE and death was 0.5%in the rivaroxaban group (n=6183) compared with 1.0% for the enoxaparin group (n=6200); P=0.001 at day 12+/- 2. For the total study duration the incidence was 0.8% vs. 1.6%, respectively; P<0.001.
Rates of major bleeding in the head-to-head treatment pool were 0.3% for rivaroxaban and 0.2% for enoxaparin; P=0.175. The respective figures in the total study duration pool were 0.4% vs. 0.3%; P=0.135.
How does this relate to other studies?
The Scottish Medicines Consortium (SMC) has recently accepted rivaroxaban for use within NHS Scotland for the prevention of VTE in adult patients undergoing elective hip or knee replacement surgery. NICE has issued guidance on the use of oral dabigatran for VTE prophylaxis after major orthopaedic surgery and it is anticipated that they will issue guidance on rivaroxaban in June 2009.
The results of this analysis reinforce the findings of the individual, published RECORD studies that we have blogged previously. An oral drug for VTE prophylaxis has the potential to increase patient compliance and release nurse time from either administering injections or teaching patients to self-inject.