Final draft guidance from NICE recommends Xarelto (rivaroxaban) to treat pulmonary embolism (PE) and deep vein thrombosis (DVT) and prevent their recurrence.

The Bayer drug offers an alternative to warfarin, the standard treatment for dangerous internal blood clotting.

Xarelto presents fewer dose management challenges than warfarin, and has fewer interactions with other drugs and with foods.

DVT, an abnormal blood clot formation in the leg or pelvis, can lead to PE and other dangerous circulatory malfunctions that cause disability or death. Risk factors for DVT include prolonged travel and/or immobility.

Suspected PE is treated with an anticoagulant, usually initial injections of heparin followed by longer-term oral doses of warfarin. However, warfarin presents complex dose adjustment challenges and can interact dangerously with other medications and with foods.

NICE determined that Xarelto was cost-effective both as a treatment for PE and DVT over three, six or 12 months and as a lifelong treatment to prevent the recurrence of PE or DVT.

Professor Carole Longson, NICE Health Technology Evaluation Centre Director, said: “The regular monitoring and dose adjustment needed with warfarin, which needs regular visits to hospital or GP appointments, can be costly and inconvenient. Also, because warfarin has many drug interactions, it may be unsuitable for people with comorbidities. In addition, the Committee heard that warfarin has various food interactions which often require people to adjust and monitor their diet.

“Rivaroxaban therefore represents a significant potential benefit for people with PE and DVT because it avoids the need for initiation with heparin and the subsequent transition to warfarin.”

Final NICE guidance is expected in May 2013.

The Scottish Medicines Consortium (SMC) has accepted Eliquis (apixaban) for prevention of strokes in patients with atrial fibrillation (AF).

The drug, produced by Pfizer and Bristol-Myers Squibb (BMS), has also been provisionally recommended by NICE.

Its use in Scotland with AF patients over 40 is predicted to prevent nearly 1,000 strokes and over 300 deaths per year.

Following its EMA approval in November 2012, the SMC has accepted Eliquis for prevention of strokes in patients with non-valvular AF who have one or more risk factors (e.g. hypertension, diabetes).

Based on recent clinical trials, the SMC said Eliquis was superior to warfarin in preventing strokes and was associated with fewer major bleeds.

It also requires no monitoring and dosage adjustment, thus reducing the cost of treatment and avoiding the risks associated with poor monitoring.

AF affects over 60,000 people in Scotland over the age of 40. It causes a fivefold increase in stroke risk, resulting in 7% of all strokes. Strokes due to AF are more severe, and more likely to recur, than strokes with other causes.

Difficulties in setting the dosage of warfarin, the standard anticoagulant, mean that fewer than half of Scottish AF patients at high risk of stroke are receiving it.

Dr Derek Connelly, Consultant Cardiologist at the Royal Infirmary, Glasgow, said: “The SMC acceptance of apixaban is an important step forward for patients with atrial fibrillation in Scotland. The availability of a new treatment option that does not require [clotting time] monitoring may help decrease the impact atrial fibrillation has on the quality of life of patients, their families and carers.”

According to Amadou Diarra, BMS General Manager, UK and Ireland, the risk of stroke in patients with non-valvular AF is “a serious public health concern” that Eliquis can help to address.

NICE has provisionally recommended Eliquis in the same indication, with final guidance expected shortly.

The alliance between BMS and Pfizer to develop drugs against cardiovascular disease began in 2007.

UK Science Minister David Willetts intervened with NHS leaders to promote AstraZeneca’s anticoagulant Brilique (ticagrelor).

According to the department for Business, Innovation and Skills (BIS), Willetts was acting within his remit of “strategic relationship management”.

However, a Cass Business School expert has suggested that his action on behalf of the pharma company was anti-competitive.

Brilique is recommended by NICE for prevention of strokes and heart attacks in patients with unstable angina, but take-up of the medicine has been uneven.

Vanessa Rhodes, a spokeswoman for AstraZeneca, justified the company’s action: “Despite this recommendation and the NHS target of reducing the mortality rate from cardiovascular disease, it is currently only routinely available to patients in some parts of England.

“We share the NHS and the government’s objective of broadening patient access to innovative medicines.”

After Willetts’ intervention was reported in The Times, BIS issued a press release explaining: “He regularly meets with companies to discuss issues of importance to them, and has a strong interest in making sure that the environment for the life-sciences industry is conducive to innovation and growth.”

AstraZeneca is undergoing major austerity measures under new chief executive Pascal Soriot, who has said the heads of R&D and global commercial operations will leave the company at the end of this month.

Willetts’ action could be justified as an attempt to enforce the Government’s innovation strategy by ensuring that NICE-recommended drugs are available through the NHS, or as an attempt to protect British jobs.

However, Stefan Haefliger, Lecturer in Strategic Management and Innovation at London’s Cass Business School, said it was merely commercial lobbying.

Politicians “are supposed to support the best drug for the patient and not promote local jobs,” he argued.

The European Medicines Agency (EMA) has requested a label update to provide clearer guidance on the safe use of the anticoagulant Pradaxa (dabigatran).

The review has confirmed the drug’s positive benefit-risk balance as a stroke prevention treatment for certain patients, but stated the need for clearer notes on the medicine’s risks and what to do in case of bleeding.

The Boehringer Ingelheim drug is recommended for patients with non-valvular atrial fibrillation or following hip or knee replacement.

Because all blood-thinning drugs can cause bleeding, the EMA has maintained close post-market surveillance of this product.

The EMA’s scientific advisory committee, the CHMP, found that the incidence of fatal bleedings with Pradaxa in post-marketing data was significantly lower than in the clinical trials that led to the drug’s authorisation in 2008.

In November 2011, a safety review concluded that the drug should be used with caution, and at lower doses, with patients who were elderly or had moderate renal impairment.

Pradaxa “remains an important alternative to other blood-thinning agents,” the EMA said.

However, the guidance for doctors and patients should be strengthened to include details of the risks, when the drug must not be used, and how to manage patients if bleeding occurs.

In particular, patients taking Pradaxa should seek urgent medical attention of they fall or suffer any injury.

The European Commission is expected to confirm this opinion.

Boehringer Ingelheim’s anticoagulant Pradaxa (dabigatran etexilate) has been shown by a phase III clinical trial to be safer than warfarin, the standard stroke prevention drug.

The global 18,000-patient RE-LY trial showed significantly lower rates of fatal and traumatic intracranial haemorrhage (ICH) in patients treated with Pradaxa rather than with well-controlled warfarin.

The new findings suggest that Pradaxa may offer an alternative to warfarin in patients with atrial fibrillation (AF), easing the burden of dosage adjustment.

AF is experienced by one in four adults over the age of 40, and is a major risk factor for strokes. Anticoagulation therapy is widely used as a preventative measure – but ICF is a widespread side-effect, causing disability and death.

Warfarin (first introduced in 1948 as a rodent poison) is the standard treatment for prevention of strokes. However, very careful dosage adjustment is needed to minimise the risk of ICF.

The RE-LY trial evaluated 154 intracranial haemorrhages that occurred in 153 patients during the trial period, comparing the effects of Pradaxa and well-controlled warfarin:

• Pradaxa 110mg and 150mg doses were associated with significantly fewer fatal ICH events (11 and 13 respectively vs. 32) than warfarin.

• Pradaxa was associated with significantly fewer traumatic ICH events (11 vs. 24) than warfarin.

• The rate of ICH with Pradaxa was similar to the rate in patients receiving antiplatelet therapy.

Dr Stuart Connolly, Director of the Division of Cardiology at McMaster University, Hamilton, Ontario, said: “In our hospital, we see patients frequently presenting with intracranial haemorrhage as a result of warfarin and unfortunately, this complication is associated with a high mortality rate.

“These data show us that not only is Pradaxa associated with lower rates of intracranial haemorrhage overall, but that fatal and traumatic intracranial bleeding is also reduced, highlighting the favourable safety profile of Pradaxa.”

Boehringer Ingelheim has reduced the UK price of its oral anticoagulant Pradaxa (dabigatran etexilate) by 13%, two weeks after receiving NICE recommendation.

While NICE had judged Pradaxa to be cost-effective for stroke prevention in patients with atrial fibrillation (AF) at £2.52 per day, the new price of £2.20 will increase its appeal to prescribers.

The timing of the price change reflects growing industry awareness that NICE approval is only a step on the way to meeting the value criteria of the NHS.

The final NICE guidance recommended that Pradaxa be considered for the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (AF) with one or more risk factors, a potential 900,000 people.

The price drop will help to drive access to the first new oral anticoagulant for stroke prevention in patients with AF in 60 years.

According to a recent BMJ report, drug therapy for stroke prevention in patients with AF is sub-optimal in many cases. Up to 30% receive no treatment, a significant proportion of those treated with warfarin are not well controlled, and treatment with aspirin is not adequate.

There is therefore a large unmet need for effective stroke prevention treatment in these patients, whose risk of stroke may be significantly reduced by Pradaxa.

Duncan Cantor, Boehringer’s Director of Communications, said: “We are committed to working with the NHS to offer the very best value we can. Although NICE deem Pradaxa to be cost effective at £2.52 per day, we believe it is important to make our medicines as affordable as possible in this tough financial climate.

“By lowering the price by 13% to £2.20, the NHS now has every opportunity to make sure this medicine is available to all eligible patients.”

NICE has recommended the use of Pradaxa (dabigatran) as an option for the prevention of stroke and systemic embolism in people with atrial fibrillation (AF) in final guidance.

The treatment is the first new oral-anticoagulant in nearly 60 years to be recommended after NICE concluded it was more effective than warfarin.

Boehringer Ingelheim called the appraisal a “landmark decision”.

The recommendation comes after a failed appeal on the draft guidance by NHS Salford who argued that NICE had failed to act fairly and had exceeded its powers.

It claimed NICE had underestimated the likely use of Pradaxa and that its recommendation would require a design overhaul of anticoagulant services at a PCT level.

But its objections were dismissed on all points by an independent Appeal Panel chaired by NICE’s chair Professor Sir Michael Rawlins.

The guidance recommends Pradaxa as a treatment option in accordance with its licensed indications, and that treatment should start after an informed discussion about its risks and benefits compared with warfarin.

Pradaxa has a UK marketing authorisation for the prevention of stroke and systemic embolism in adults with nonvalvular AF who have previously suffered a stroke, transient ischaemic attack or systemic embolism and other heart related problems. It is also authorised for those aged 65 years old or over with AF who have diabetes, coronary heart disease or hypertension.

It’s estimated that there are around 700,000 people with AF in England and Wales. Boehringer believes that the use of Pradaxa twice daily has the potential to prevent around 530 more strokes per 100,000 compared to warfarin. And, if all eligible patients received Pradaxa twice daily, it could prevent up to 5,000 strokes and save the NHS up to £59 million in the first year of use.

Charles De Wet, Medical Director at Boehringer Ingelheim, said “We are committed to sharing value and our priority and commitment now is to work closely with the Trusts to ensure dabigatran is accessible to all eligible patients on the NHS and appropriately prescribed by clinicians”.

The use of prescribed aspirin is not suitable for primary prevention of cardiovascular diseases, according to a new UK-led study.

The study found that a small reduction in heart attack risk achieved by regular aspirin doses was outweighed by a greater increase in the risk of serious internal bleeding.

The authors concluded that regular prescription of aspirin in people with no history of cardiovascular disease is not appropriate.

A research team at St George’s University of London analysed data from nine clinical trials with over 100,000 healthy people over six years to determine the effects of taking aspirin daily.

Regular aspirin doses reduced the total incidence of cardiovascular events by 10%, but this difference was entirely in non-fatal heart attacks and not in strokes or fatal heart attacks.

In addition, regular aspirin doses increased the incidence of severe or potentially fatal internal bleeding by 30%.

Aspirin, a mild anticoagulant, has been shown to reduce the risk of blood clotting. It is widely prescribed in both secondary and primary prevention of cardiovascular events.

The study authors concluded that since the risks outweigh the benefits, “routine use of aspirin for primary prevention is not warranted”.

Lead study author Dr Rao Seshasai emphasised that the use of aspirin in secondary prevention of cardiovascular disease (in people with a history of such disease) is undoubtedly worthwhile.

However, he noted, the benefits of aspirin to patients without a history of cardiovascular disease are “far more modest” and the risks greater than had been thought.

“It would be worthwhile to review the existing recommendations, such as the Joint British Societies' Guidelines, for the use of this agent in low-risk populations, and consider aspirin treatment more selectively on a case-by-case basis,” he said.

More effective diagnosis and treatment of atrial fibrillation (AF) is needed to prevent an ‘epidemic’ of strokes, according to a new report from the Atrial Fibrillation Association (AFA) and AntiCoagulation Europe.

The health charities noted that AF affects 1 in 4 people in the UK and causes 45% of embolic strokes, but only 18% of AF patients in the UK receive drug therapy that could help to prevent stroke.

Better use of anticoagulants such as Pradaxa could help to prevent many of the 12,000 strokes caused by AF in the UK every year, the AF Report said.

The report warned that the incidence of AF is expected to more than double in the next 40 years – leading to a major increase in the frequency of embolic strokes (caused by blood clots), the most damaging type of stroke.

To prevent a stroke ‘epidemic’, the report said, a number of measures are necessary, including:

• a targeted programme of routine pulse checks by GPs

• equal access to AF treatments and services, regardless of location

• improved GP awareness of the need for patient education and appropriate referral, supported by a public education programme

• support for research into the causes, prevention and treatment of AF.

The AFA has launched a public-access website at www.afstrokerisk.org, enabling people diagnosed with AF to assess their risk of stroke by answering simple questions.

“The detection of AF and subsequent prevention of stroke with appropriate anticoagulant treatment must be a key priority in health services,” said Eve Knight, CEO of AntiCoagulation Europe. “If existing guidelines were followed, then many more at-risk AF patients would receive the life-saving anticoagulation that they need.

“With the addition of routine pulse checks we could revolutionise detection and management of AF.”

Eliquis (apixaban), an oral drug from Pfizer and Bristol-Myers Squibb for the prevention of venous thromboembolism (VTE) in acutely ill patients, has failed to meet the required endpoint in a Phase 3 clinical study.

In the ADOPT trial, Eliquis did not meet the primary efficacy outcome of superiority to enoxaparin in preventing VTE and VTE-related death.

Eliquis performed 13% better than enoxaparin in preventing VTE events, which was not statistically significant, over 30 days.

Major bleeding, a key safety outcome, occurred more often with Eliquis than with enoxaparin but had a low frequency (0.47% and 0.19% respectively) in both groups.

VTE encompasses two dangerous events: pulmonary embolism and deep vein thrombosis (which can lead to pulmonary embolism).

Eliquis, an anticoagulant, is a direct factor Xa inhibitor and is currently approved in the EU for the prevention of VTE in adult patients who have undergone hip or knee replacement surgery.

ADOPT (Apixaban Dosing to Optimise Protection from Thrombosis) was a Phase 3, international, multi-centre, randomised, double-blind, controlled study comparing apixaban with enoxaparin in acutely ill patients.

Over 30 days, VTE events occurred in 2.71% of patients in the Eliquis group and 3.06% of patients in the enoxaparin group. Overall, the outcomes for both patient groups were similar.

Dr. Samuel Z. Goldhaber, senior cardiologist at Brigham and Women’s Hospital, commented: “ADOPT provides important insights for clinical trialists designing studies of extended duration VTE prophylaxis among medically ill hospitalised patients.

“Solving the problem of VTE post-hospitalisation remains a critical unmet need in preventing medically ill patients from developing deep vein thrombosis and pulmonary embolism.”

Eliquis has been co-developed by Pfizer and Bristol-Myers Squibb since 2007, following its discovery by BMS.