In final draft guidance published today (1 June), NICE has recommended rivaroxaban (Xarelto, Bayer Healthcare) as an option for treating deep vein thrombosis and preventing recurrent deep vein thrombosis and pulmonary embolism in adults diagnosed with acute deep vein thrombosis (DVT). Publication of the draft recommendation follows receipt of further information from the manufacturer that had been requested by NICE in its previous draft guidance.

Venous thromboembolism (VTE) is the term used to describe a condition in which a blood clot (a thrombus) forms in a vein and then dislodges to travel in the blood (an embolus). A venous thrombus most commonly occurs in the deep veins of the legs or pelvis; this is called deep vein thrombosis (DVT). Blood flow through the affected vein can be limited by the clot, and it can cause swelling and pain in the leg. If the thrombus dislodges and travels to the lungs, this can lead to a potentially fatal pulmonary embolism (PE) when the clot blocks the blood supply to the lungs. Other complications of DVT include post-thrombotic syndrome, a chronic disorder that may include symptoms such as pain, heaviness, swelling, cramps, itching or tingling, increased skin pigmentation and ulceration in the affected limb.

Risk factors for VTE include a history of DVT (people with a previous episode of VTE have a high (30%) chance of suffering a recurrence within 8 years), recent surgery, immobility, active cancer or cancer treatment, age over 60 years, obesity, hormone replacement therapy or oestrogen containing contraceptive therapy and the presence of co-morbidities such as heart disease. It is estimated that there will be over 46,000 cases of acute DVT in England and Wales during 2012, rising to nearly 50,000 by 2016 due in large part to the aging population.

Treatments for VTE include initiation with injectable anticoagulants such as low-molecular-weight heparin or fondaparinux sodium. Treatment is then overlapped with a vitamin-K antagonist, such as warfarin, until effective anticoagulation with the oral agent is achieved.

Rivaroxaban is an orally administered drug that helps to prevent blood from clotting. It does this by stopping a substance called Factor Xa from working. Factor Xa is necessary in the formation of thrombin and fibrin, the key components in blood clot formation. Duration of treatment with rivaroxaban is based on an assessment of the benefit of anticoagulation compared with the risk of bleeding and usually ranges from 3 to 12 months. Some people with ongoing risk factors for recurrence of VTE need ongoing treatment, possibly for many years or lifelong.

Professor Carole Longson, NICE Health Technology Evaluation Centre Director, said: "For many people, using warfarin is difficult because of the need for regular monitoring with blood tests, dosing adjustments, and the need to be careful about their diet because of warfarin's interaction with certain foods. The independent Appraisal Committee was initially unable to recommend rivaroxabanbased on the data presented by the manufacturer because it did not adequatelydemonstrate the drug's clinical and cost effectiveness in the context of UK clinical practice. We are pleased to say that, following the submission of additional information and analysis from the manufacturer during consultation, the committee is able to recommend rivaroxaban as a cost-effective option for treating DVT and preventing recurrent DVT and PE in adults."

The draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues final guidance, NHS bodies should make decisions locally on the funding of specific treatments.

ENDS

Notes for Editors

About the draft guidance

1. The draft guidance is available (from 1 June) on the NICE website at TA261. Please contact the NICE press office for an embargoed copy of the draft guidance.

2. The Committee noted that rivaroxaban dominated dual low-molecular-weight heparin and a vitamin K antagonist in the 3 month group; the ICER for rivaroxaban was £3200 per QALY gained for the 6 month treatment duration and £14,900 per QALY gained for the 12 month treatment duration.The ICER for rivaroxaban was £19,400 per QALY gained for people who require anticoagulation beyond 12 months of treatment.

3. Rivaroxaban costs £2.10 per 15 mg or 20 mg tablet. The cost of treatment is estimated to be £235.86, £427.61 and £811.13 for 3, 6 and 12 months of treatment respectively. Costs may vary in different settings because of negotiated procurement discounts.

4. The previous draft guidance requested that the manufacturer provide further information on a number of key aspects of the appraisal, including the following:

• Comments on the differences between the populations that were assigned treatment durations of 3, 6 and 12 months, and further details of any clinical criteria or algorithm used by the treating physician for assigning patients to the three groups.
• Consideration of the cost effectiveness of rivaroxaban compared with low-molecular-weight heparin and a vitamin K antagonist in patients in whom long-term anticoagulation is intended. Ideally this should be supported by a cost-effectiveness analysis of rivaroxaban as a lifelong treatment after the index event. This analysis should use data from the whole population of the EINSTEIN-DVT trial for estimating clinical effectiveness and should include sensitivity analyses that assume a less intensive INR monitoring program of 6 visits in the first 3 months, followed by 2 or 3 visits every 3 months thereafter in the comparator arm.

5. From the additional information received from the manufacturer, the Committee concluded that:

• Patients recruited into the trial were allocated to 3, 6 and 12 month treatment durations by the treating physician, based on individual patient risk factors, before randomisation.
• There were no specific clinical criteria or algorithm used to allocate people into the different intended treatment duration groups, and that there was no apparent biological or clinical plausibility for the differential effectiveness of rivaroxaban across the intended treatment duration subgroups. The Committee therefore concluded that evidence of treatment effect should be based on the whole trial population of EINSTEIN-DVT and that rivaroxaban was more clinically and cost effective than enoxaparin followed by a vitamin K antagonist for preventing recurrent VTE in people in whomtreatment for up to 12 months is indicated.
• With the committee's preferred assumptions the ICER for long term treatment was below £19,400 per QALY gained.

6. The Scottish Medicines Consortium published guidance on the use of rivaroxaban for this indication in February 2012.

7. NICE has appraised rivaroxaban for the prevention of venous thromboembolism after total hip or total knee replacement in adults. NICE technology appraisal guidance 170 (2009).

8. NICE has also published guidance recommending rivaroxaban as an option for the prevention of stroke in people with atrial fibrillation.

About NICE

9. The National Institute for Health and Care Excellence (NICE) is the independent organisation responsible for providing national guidance and standards on the promotion of good health and the prevention and treatment of ill health

10. NICE produces guidance in three areas of health:

• public health - guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector
• health technologies - guidance on the use of new and existing medicines, treatments, medical technologies (including devices and diagnostics) and procedures within the NHS
• clinical practice - guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.

11. NICE produces standards for patient care:

• quality standards - these reflect the very best in high quality patient care, to help healthcare practitioners and commissioners of care deliver excellent services
• Quality and Outcomes Framework - NICE develops the clinical and health improvement indicators in the QOF, the Department of Health scheme which rewards GPs for how well they care for patients

12. NICE provides advice and support on putting NICE guidance and standards into practice through its implementation programme, and it collates and accredits high quality health guidance, research and information to help health professionals deliver the best patient care through NHS Evidence.