Data from the pivotal phase III RECORD4 clinical trial, published online in The Lancet demonstrate that Bayer’s novel anticoagulant Xarelto (rivaroxaban), taken as one tablet, once-daily, was significantly more effective at reducing the occurrence of venous blood clots following elective total knee replacement surgery (TKR) than twice-daily injectable, enoxaparin.
These results make Xarelto the only oral anticoagulant to have demonstrated superior efficacy compared to enoxaparin at its higher US-approved dosing regimen of 30mg twice-daily for venous thromboembolism (VTE) prevention in patients undergoing TKR.
Professor Beverley Hunt, Consultant Haematologist and Medical Director of Lifeblood: The Thrombosis Charity, welcomes the promising RECORD4 trial results, she said: “We want to ensure that every adult admitted to hospital in the UK receives appropriate prevention against hospital-acquired clots, which are the number one cause of preventable deaths in hospital care.
We welcome rivaroxaban which has the advantages of being a tablet and has proven to be superior to the gold standard in clinical trials after knee replacements”
In addition to these efficacy advantages, rivaroxaban has other benefits compared with currently available treatment options because it is given as a one tablet, once-daily, fixed-dose regimen that eliminates the need for any routine monitoring (such as clotting, liver function etc) or dose adjustment.
Venous thromboembolism (VTE) is a leading cause of preventable hospital deaths in the UK, causing 10 per cent of all deaths from hospital stays – up to 32,000 people each year – more than HIV/AIDS, breast cancer, and road traffic accidents combined.
Major orthopaedic surgery is associated with a particularly high risk of hospital-acquired VTE – more than half of the 90,434 people undergoing elective hip or knee replacement every year in England could develop a potentially fatal blood clot if no preventative treatment (known as thromboprophylaxis) is given.
RECORD4 forms part of the RECORD clinical trial programme, which involved more than 12,500 elective total hip or knee replacement surgery patients. Data from the RECORD programme supported the approval of Xarelto by the European Commission in October 2008, and positive SMC and NICE recommendations in December 2008 and April 2009 respectively.
The full RECORD data set was also used to support the new drug application for Xarelto in the US in 2008, as well as additional filings that are under review with regulatory agencies around the world.
RECORD4 was a multicentre, randomised, double-blind trial that compared oral Xarelto (10 mg tablet once-daily) with the US-approved enoxaparin regimen (30 mg injection twice-daily) for the prevention of VTE following TKR surgery in 3,148 patients. Xarelto provided patients with the following benefits over enoxaparin:
- A statistically significant reduction in VTE event rates, 6.9 % vs. 10.1 %
- A relative risk reduction (RRR) of 31 % in total VTE rates (composite of deep vein thrombosis, non-fatal pulmonary embolism and all-cause mortality)
Furthermore, Xarelto maintained a similar low rate of major bleeding that was not statistically different to the rate of major bleeding in the enoxaparin-treated patients.
Professor Ajay Kakkar, Professor of Surgical Sciences at the Barts and the London School of Medicine and Dentistry, and Director of the Thrombosis Research Institute, London said, “Blood clots after major orthopaedic surgery remain a serious clinical problem. Data from the RECORD4 study confirm the efficacy and safety of the novel anticoagulant rivaroxaban, demonstrated in three previous studies. Rivaroxaban will add to our armamentarium of thrombosis-preventing strategies and help in their use after hospital discharge.”