NICE Recommends Xarelto(R) (rivaroxaban) Use In NHS, UK

Main Category: Blood / Hematology
Article Date: 23 Apr 2009 - 3:00 PDT

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Without preventative treatment, 45,000 people undergoing elective hip or knee replacement every year in England could develop a potentially fatal blood clot. NICE now recommends Xarelto - a new, oral anticoagulant, up to 70% more effective at reducing blood clots than the current gold standard (injectable enoxaparin).

The National Institute for Health and Clinical Excellence (NICE) has today recommended the new oral anticoagulant Xarelto® (rivaroxaban), within its licensed indication, as a treatment option for the prevention of potentially fatal blood clots (venous thromboembolism) in adults undergoing elective hip or knee replacement surgery. After a large scale clinical trial programme involving over 12,500 patients, Xarelto has a wealth of evidence supporting its clinical and cost-effectiveness and has received this positive appraisal from NICE within seven months of its launch in the UK.1

Until recently, anticoagulant therapy often required administration by injection and little had advanced in terms of new treatments for over fifty years.2 Two new oral anticoagulants came to market during 2008, each working in a different way. Xarelto - an oral direct Factor Xa inhibitor - is the first of a new generation of oral anticoagulants and the first to demonstrate superior efficacy to the current standard of care, injectable enoxaparin, whilst maintaining a comparable side-effect profile.3,4

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.5 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 England6 could develop a potentially fatal blood clot if no preventative treatment (known as thromboprophylaxis) is given.7

Professor Beverley Hunt, Consultant Haematologist and Medical Director of Lifeblood: The Thrombosis Charity, welcomes NICE's positive decision: "It is terrific that NICE has approved Xarelto so quickly. A new highly effective oral anticoagulant will encourage thromboprophylaxis implementation and greatly reduce the risk of hospital-acquired clots after planned major orthopaedic surgery."

In a large-scale Phase III clinical trial programme involving over 12,500 patients, rivaroxaban became the first oral anticoagulant to demonstrate superior efficacy over the current standard of care (injected enoxaparin). In these trials, rivaroxaban reduced the combined total of VTEs and deaths by between 49-70%.3,4,8 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 coagulation (clotting), liver function etc) or dose adjustment.9

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, "NICE's recommendation about rivaroxaban is very positive. Venous thromboembolism is the commonest avoidable cause of hospital death. Today's announcement means we have another effective method to prevent potentially fatal blood clots in orthopaedic surgical patients. In particular we can now facilitate the use of preventative methods out of hospital."

VTE costs the NHS an estimated £640 million per year.5 A further £19 million of NHS money is spent on litigation from patients who have developed blood clots as a result of a hospital stay or procedure.10

About hospital-acquired DVT

-- Venous blood clots, (also known as venous thromboembolism or VTE) can take the form of either:

- A deep vein thrombosis (DVT) - a blood clot in a deep vein (usually in the leg) that partially or totally blocks the flow of blood11
- A pulmonary embolism (PE) - a blood clot blocking an artery in the lungs11

-- Each year up to 32,000 people in the UK die from venous blood clots as a result of a hospital stay or surgical procedure (sometimes referred to as 'hospital-acquired DVT'). This is more people than die from breast cancer, HIV/AIDS and road traffic accidents combined5

-- Many of these deaths could be prevented5

-- Effective prevention and treatment of hospital-acquired DVT is a major national public health issue5

-- People at risk of hospital-acquired DVT include people undergoing major orthopaedic surgery and those who are hospitalised or immobilised over long periods 12,13

-- The majority (74%) of hospital-acquired DVT cause symptoms after the patient has left hospital13

-- Hospital-acquired DVT occur in up to 50% of patients undergoing major orthopaedic surgery who do not receive preventative care7

-- In November 2008, the All-Party Parliamentary Thrombosis Group (APPTG) published their second annual report which showed that 70% of acute hospital trusts are now taking steps to risk assess patients for hospital-acquired DVT14 - compared with only 32% in their 2007 report.15 These findings demonstrate that more hospitals are now bringing their practices in line with NICE and government recommendations, which are as follows:

- Current NICE recommendations state that:16

- All patients undergoing major surgery should be assessed to identify their individual risk of developing VTE after the procedure

- All patients undergoing major orthopaedic surgery of the lower limbs should receive anticoagulant therapy, LMWH (low molecular weight heparin) for up to 28 days after surgery in combination with pressure stockings, to reduce the risk of VTE

- SIGN guidelines recommend patients undergoing total hip or knee replacement surgery should be considered for both pharmaceutical thromboprophylaxis for up to five weeks following surgery, and mechanical methods of thromboprophylaxis17

About Xarelto® (rivaroxaban)

Xarelto® is licensed for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery. It is the first of a new class of oral anticoagulant specifically inhibiting Factor Xa, a pivotal step in the coagulation (blood clotting) process.18

Unlike low molecular weight heparins, such as enoxaparin, which are administered daily by injection, Xarelto® is an oral, one tablet once-daily treatment which is administered six to ten hours after surgery.19 It is licensed for two weeks following elective knee replacement surgery or five weeks following elective hip replacement surgery. An oral tablet such as Xarelto® offers a more convenient, patient orientated treatment option than an injection as it enables patients to more easily continue their anticoagulant therapy at home, providing ongoing protection against the continued risk of developing clots. Further, there are no routine coagulation monitoring requirements with Xarelto®.

More than 60,000 patients are expected to be enrolled into the Xarelto clinical development program, which will evaluate the product in the prevention and treatment of a broad range of acute and chronic blood-clotting disorders.

References

1. Rivaroxaban for the prevention of venous thromboembolism after total hip or total knee replacement in adults. April 2009. http://www.nice.org.uk/nicemedia/pdf/TA170Guidance.pdf (last accessed 22 April 2009)

2. New Blood Thinner - First Potential Alternative to Warfarin in 50 years. Bio-Medicine (last accessed 07.04.09)

3. Eriksson BI et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008; 358 (26): 2765-2775

4. Lassen MR et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008;358:2776-86

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

6. National Joint Registry. (last accessed 13.02.09)

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

8. Kakkar AK et al. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthoplasty: a double-blind, randomised controlled trial. The Lancet. 2008; 372(9632):31-39

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

10. Scurr JHR et al. Is failure to provide venous thromboprophylaxis negligent? Phlebology 2007; 22: 186 - 191

11. Lifeblood: The Thrombosis Charity. Ten questions about thrombosis. 2008. (Last accessed on 28.08.08)

12. Heit JA. The Epidemiology of Venous Thromboembolism in the Community: Implications for Prevention and Management. J Thromb Thrombolysis 2006; 21: 23-9.

13. Spencer FA et al. Venous Thromboembolism in the Outpatient Setting. Arch Intern Med 2007; 167: 1471-5.

14. All-Party Parliamentary Thrombosis Group (APPTG) VTE Research Report, November 2008

15. All-Party Parliamentary Thrombosis Group (APPTG) VTE Research Report, November 2007

16. NICE Clinical Guideline 46. Quick Reference Guide. Venous Thromboembolism: Reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in inpatients undergoing surgery. April 2007

17. SIGN Guideline No.62. Prophylaxis of Venous Thromboembolism. October 2002.

18. Turpie A et al. Comparison of rivaroxaban - an oral, direct factor Xa inhibitor - and subcutaneous enoxaparin for thromboprophylaxis after total knee replacement (RECORD4: a phase 3 study). European Federation of National Associations of Orthopaedics and Traumatology 2008 Annual Meeting; May 29-June 1, 2008; Nice, France. Abstract F85.

19. Rivaroxaban SmPC October 2008

Source
Bayer Schering Pharma UK

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