Once-Daily Oral Xarelto Significantly More Effective At Reducing Blood Clots Than Twice Daily Subcutaneous, Enoxaparin

Main Category: Blood / Hematology
Also Included In: Clinical Trials / Drug Trials
Article Date: 07 May 2009 - 0:00 PDT

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Data from the pivotal Phase III RECORD4[1] 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.1 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.1

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.2

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.3 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 England4 could develop a potentially fatal blood clot if no preventative treatment (known as thromboprophylaxis) is given.5

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 U.S. 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 U.S.-approved enoxaparin regimen (30 mg injection twice-daily) for the prevention of VTE following TKR surgery in 3,148 patients.1 Xarelto provided patients with the following benefits over enoxaparin1:

· A statistically significant reduction in VTE event rates, 6.9 % vs. 10.1 %, (p = 0.012);
· 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, (0.7 % and 0.3 % respectively; p = 0.110).1

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 RECORD 4 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"

Developments in Thromboprophylaxis Treatments

Venous blood clots are serious complications that can impact patients undergoing major orthopaedic surgery due to vascular damage and reduced mobility.6 If prophylactic measures are not taken, VTE can occur in up to 60% of these patients.7 Current treatments, such as vitamin K antagonists and heparins, have been the foundation of anticoagulation treatment for years. However they have significant disadvantages both in the outpatient setting and for long-term use. This highlights the need for development of new anticoagulants that are well tolerated and effective, but do not require regular injections or routine blood monitoring. Xarelto is taken as one tablet, once-daily (at home and in hospital), and requires no routine coagulation monitoring.8 It works by targeting a pivotal stage in the blood clotting process and directly inhibits the enzyme Factor Xa to ensure the natural healing process can still occur.8,9

The efficacy of Xarelto and low risk of bleeding demonstrated in the RECORD4 trial results were also seen in the RECORD1, 2 and 3 studies that compared Xarelto against enoxaparin (40 mg injected once-daily) after major orthopedic surgery.10,11,12

"The publication of the RECORD4 data highlights again how Xarelto continues to exceed our expectations, and is a testament to the consistently strong results generated across the full RECORD programme," said Frank Misselwitz, MD, Head of Cardiovascular Development, Bayer Schering Pharma. "With its unique targeted inhibition of Factor Xa and robust safety profile, Xarelto could transform treatment approaches for the prevention of potentially life-threatening blood clots following hip or knee replacement surgery."

[1](REgulation of Coagulation in major Orthopedic surgery reducing the risk of Deep Vein Thrombosis and Pulmonary Embolism)4: RECORD4 is the first trial to use the US regimen, comparing once-daily oral Xarelto with twice-daily enoxaparin

References:

1. Turpie AG, Lassen MR, Davidson BL et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty: RECORD4, a randomised controlled trial. The Lancet

2. Rivaroxaban 10mg film-coated tablets (Xarelto®) No. (519/08) Scottish Medicines Consortium. 07 November 2008

3. The House of Commons Health Committee. 2005. The Prevention of Venous Thromboembolism in Hospitalised Patients.

4. National Joint Registry. (last accessed 13.02.09)

5. Geerts WH et al. Prevention of Venous Thromboembolism: ACCP Guidelines 8th Edition Chest 2008;133:381-453S

6. Di Minno G, Agnes R; Tufano A. Venous thromboembolism: which patients are truly at risk? Acta Biomed 2005; 76 (Suppl 1): 31-2.

Source
Bayer Schering Pharma

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