NICE Guidance Recommends New Treatment Option for People with Common Heart Condition
In final guidance published today (15 March) NICE has recommended dabigatran (Pradaxa, Boehringer Ingelheim), in accordance with its licensed indications, as an option for the prevention of stroke and systemic embolism in people with atrial fibrillation. The guidance also recommends that the decision about whether to start treatment with dabigatran should be made after an informed discussion about the risks and benefits of dabigatran compared with warfarin, and in light of a person's current level of international normalised ratioi (INR) control if they are already taking warfarin.
Publication of the final guidance follows the dismissal on all points of an appeal against the draft guidance.
Atrial fibrillation occurs when the electrical impulses controlling the heart rhythm become disorganised, so that the heart beats irregularly and, occasionally, too fast and so cannot efficiently pump blood around the body. People with atrial fibrillation are at higher risk of developing blood clots and subsequent stroke - however, the risk of stroke can be substantially reduced by appropriate use of antithrombotic therapy (e.g. warfarin).
Dabigatran is an orally administered anticoagulant that inhibits the formation of the thrombin enzyme. It has a UK marketing authorisation for the prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation who have had a previous stroke, transient ischaemic attack or systemic embolism, and/or left ventricular ejection fraction below 40%, and/or symptomatic heart failure of New York Heart Association (NYHA) Class 2 or aboveii and/or are aged 75 years and over. Dabigatran also has a UK marketing authorisation for people with atrial fibrillation aged 65 years or over who have diabetes, coronary heart disease or hypertension.
Commenting on NICE's draft recommendation, Professor Carole Longson, NICE Health Technology Evaluation Centre Director, said: "Atrial fibrillation can be a distressing condition and people with it have an increased risk of suffering a stroke. Many people with the condition find it difficult to comply with the most commonly used antithrombotic, warfarin, because, among other things, it requires regular INR monitoring and dose adjustments which can cause disruption and inconvenience. Because dabigatran does not require frequent blood tests to monitor treatment it represents a useful alternative option for people with atrial fibrillation.
Professor Longson continued: "The independent Appraisal Committee accepted evidence from clinical trials that showed dabigatran 150 mg twice daily is more clinically effective than warfarin in reducing the risk of stroke or systemic embolism, and that dabigatran 110 mg twice daily is as effective as warfarin. We are pleased, therefore, to be able to recommend dabigatran as a cost-effective option for the prevention of stroke and systemic embolism in people with atrial fibrillation."
Notes to Editors
References and explanation of terms
i. A measure of how long it takes the blood to clot
ii. New York Heart Association (NYHA) classification of heart failure symptoms:
•Class I-No limitations
•Class II-Slight limitation of physical activity (symptomatically “mild” heart failure)
•Class III-Marked limitation of physical activity (symptomatically “moderate” heart failure)
•Class IV- Symptoms of heart failure are present even at rest (symptomatically “severe” heart failure)
About the guidance
1. The final guidance is available at: http://guidance.nice.org.uk/TA249 (from 15 March)
2. Estimates suggest there may be as many as 700,000 people with atrial fibrillation in England and Wales.
3. Dabigatran is an orally administered anticoagulant that inhibits the formation of the thrombin enzyme. It has a UK marketing authorisation for the prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation who have had a previous stroke, transient ischaemic attack or systemic embolism, and/or left ventricular ejection fraction below 40%, and/or symptomatic heart failure of New York Heart Association (NYHA) Class 2 or aboveii and/or are aged 75 years and over. Dabigatran also has a UK marketing authorisation for people with atrial fibrillation aged 65 years or over who have diabetes, coronary heart disease or hypertension.
4. Dabigatran is available as 110 mg and 150 mg capsules and comes in packs of 10, 30, 60 and 180 capsules. The cost to the NHS of a pack of 60 tablets is £75.60 (excluding VAT) for both 110mg and 150mg doses. The cost per day per patient based on the recommended dosage will be £2.52 (excluding VAT). Costs may vary in different settings because of negotiated procurement discounts.
5. The Committee concluded that dabigatran 150 mg twice daily was more clinically effective than warfarin in reducing the risk of stroke or systemic embolism, ischaemic stroke and vascular mortality and that this represented an important development for people with atrial fibrillation. It also concluded that the lower 110 mg dabigatran twice-daily dose had shown non-inferiority to warfarin.
6. The most plausible ICERs for the whole population eligible for dabigatran are within the range normally considered a cost-effective use of NHS resources, being less than £20,000 per QALY gained.
7. The Scottish Medicines Consortium published guidance accepting the use of dabigatran for this indication in September 2011.
8. NICE has already published guidance on dabigatran etexilate for the prevention of venous thromboembolism after hip or knee replacement surgery in adults. NICE TA157, published in September 2008, recommends the drug, within its licensed indication, as an option for the primary prevention of venous thromboembolic events in adults who have undergone elective total hip replacement surgery or elective total knee replacement surgery.
About the appeal
1. The appeal by Salford NHS against the Final Appraisal Determination (final draft) was heard on 7 February by an independent Appeal Panel Chaired by NICE Chair Professor Sir Michael Rawlins.
2. There are three grounds under which an appeal can be lodged:
•The Institute has failed to act fairly
•The Institute has formulated guidance which cannot reasonably be justified in the light of the evidence submitted
•The Institute has exceeded its powers
3. The Vice-Chair of the Appeal Committee (Dr Jonathan Tross) confirmed that the appellant, Salford NHS, had valid grounds of appeal under Ground 1 that “The Institute has failed to act fairly” as follows:
•The PCT is concerned that by not having access to primary
care professionals neither on the Technology Appraisal Committee,
nor via the professional/specialist groups or selected clinical
experts, the Committee has failed to act fairly.
4. The Appeal Panel considered that GPs had contributed to the NHS Salford response. The Panel also noted that there were comments from general practice among the published comments on the Appraisal Consultation Document. The Appraisal Committee had heard oral evidence from a Commissioner who was a GP. The Appellant could not point to necessary evidence that was missing but which could have been supplied by a GP; and did not consider that the evidence in front of the Appraisal Committee could not be understood without the further input of a GP. It therefore concluded that the Appraisal Committee had considered all relevant material and had acted fairly. The Appeal Panel therefore dismissed this appeal point.
5. The Vice-Chair of the Appeal Committee (Dr Jonathan Tross) confirmed that the appellant, Salford NHS, also had valid grounds of appeal under Ground 1 that “The Institute has failed to act fairly” as follows:
•The PCT considers that by significantly changing the
recommendation in the guidance following the initial ACD, it is
unfair to proceed straight to the FAD. This is because had PCTs or
other health care professionals identified that such a
recommendation was likely, they might have responded to NICE via
the ACD procedure. This is selectively unfair to commissioning
6. The Appeal Panel concluded that:
•Whether or not the failure to issue a second consultation
document in these circumstances might generate a valid appeal point
would depend on the facts of the appraisal. The Appeal Panel's view
is that all consultees must be taken to know that any consultation
document is by definition provisional. Any consultee who does not
respond or respond fully to a consultation exercise because they
agree with the Appraisal Committee's preliminary conclusion,
however that conclusion is expressed, does so at their peril.
However, in general terms, there is a potential risk to fairness
when a preliminary conclusion is reversed without further
consultation. In particular, if a "minded no" .......did not
contain or draw attention to the main factors which might lead a
committee to issue a positive recommendation, then there would be a
real risk of unfairness in not re-consulting. An Appraisal
Committee needs to proceed with care. However in this case the
Appraisal Consultation Document had indeed specifically indicated
the areas of particular interest to the Appraisal Committee, so
that consultees could address them.
•In this case, the evidence to support the use of the Manchester Cardiac Consortium's approach had been presented in response to the Appraisal Consultation Document; and that this had been considered by the Appraisal Committee in its discussions. It appeared to the Appeal Panel that the evidence NHS Salford would have presented, if a second Appraisal Consultation Document had been issued, would only have re-iterated this. It may be that there would have been a change of emphasis or expression, but the substance of the relevant issues had been fairly consulted on. The Appeal Panel therefore dismissed this appeal point.
7. The Chair of the Appeal Committee also confirmed that the appellant had valid grounds of appeal under Ground 2 that "The Institute has formulated guidance which cannot reasonably be justified in light of the evidence submitted" as follows:
•The PCT considers that it is unreasonable that the
Committee did not differentiate in its recommendation in this FAD between those people for whom it has been shown that dabigatran is a cost effective use of NHS resources for this indication compared to those subgroup patients for whom the ERG has shown that the use of dabigatran is not a cost effective use of NHS resources.
8. The Appeal Panel concluded that:
•In line with the Institute's Statutory Instruments, NICE
was required to take into account cost effectiveness rather than
affordability or budgetary impact. The only occasions when the
Institute might consider affordability was after an appraisal if it
proposed that the Funding Direction should be lifted when, for
practical reasons, it would be impossible for the NHS to put its
guidance into effect in the usual timescale.
•The Committee had allowed for the known concerns about the safety of dabigatran. In any case, the Institute does not have a role in policing safety, which is a regulatory issue. If the costs and disbenefits associated with any safety issue were included in the Appraisal Committee's deliberations, then the Institute has taken account of safety issues in so far as they are relevant to it.
•The Committee had discussed plausible cost-effectiveness, and reached the reasonable conclusion that dabigatran was cost-effective across the whole population of patients with atrial fibrillation eligible for treatment. The fact that alternative treatment strategies might also be cost -effective did not render this approach unjustifiable, and in any event, the Committee had merely recommended dabigatran as a treatment option. It had explicitly stated that the decision on whether to treat with dabigatran in any individual case was to be taken only after an informed discussion between clinician and patient about the comparative risks and benefits of dabigatran and warfarin. It would be wrong to read the FAD as requiring dabigatran to be prescribed in all cases.
•The budgetary impact was not a matter with which the Appraisal Committee was or could be concerned.
The Appeal Panel therefore dismissed this appeal point.
9. The full appeal decision is available on the NICE website at http://guidance.nice.org.uk/TA/Wave21/10
1. The National Institute for Health and Clinical 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
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•public health - guidance on the promotion of good health
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This page was last updated: 14 March 2012
Posted: March 2012
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