Exclusive GPs could be restricted from prescribing dabigatran, the first new class of anticoagulant to be licensed in the UK for 50 years, to elderly patients under plans submitted to NICE.
The use of dabigatran, a direct thrombin inhibitor, in patients with atrial fibrillation is currently the subject of an ongoing technology appraisal process by NICE, with a draft recommendation expected in the autumn.
But during a public meeting of the technology appraisal committee that will decide on whether to approve the drug for use in the NHS, NICE experts heard the drug, which is available in two doses, could have a licence that restricts its use to the lower dose in the over-80s.
Such a move could throw into doubt the likelihood that the drug would be recommended at all for use on the NHS, because of modelling suggesting it would be much more cost-effective if used at the higher dose in younger patients.
If approved for use in the NHS as a treatment option for the estimated 1.2 million people in the UK who have atrial fibrillation, it is expected that dabigatran would be used predominantly in primary care as an alternative to warfarin, with secondary care experts predicting the majority of patients currently managed in hospital anticoagulation clinics could be shifted to primary care.
The bulk of the evidence for the use of dabigatran for atrial fibrillation comes from the RE-LY trial in 18,000 patients, published in September 2009, which found a 150mg dose significantly reduced the risk of stroke and systemic embolism by 34% more than warfarin and reduced the risk of a major bleed by 7%, although this was not statistically significant.
In the trial, the 110mg dose of dabigatran reduced strokes by around the same as warfarin, but reduced the risk of a major bleed by 20% more than warfarin.
The draft product label due to be issued by the European Medicines Agency is expected to restrict the 110mg dose to use only in patients over 80 – as evidence from the RE-LY trial suggested these patients have a higher bleeding risk.
But restricting elderly patients to a lower dose results in huge differences to the cost-effectiveness calculations. According to an initial cost-effectiveness analysis by NICE, only one scenario – the use of the 150mg dose of dabigatran – met the NICE threshold at £24,173 per quality-adjusted life year (QALY).
NICE experts estimated that using a 150mg dose of dabigatran and then switching patients down to the 110mg dose once they reach 80 is associated with a cost to the NHS far in excess of the usual £30,000 per QALY threshold applied to NICE technology appraisals - though a NICE spokesperson later admitted their initial calculations were incorrect and would not be used to inform the Committee's decision making.
Committee chair Dr Jane Adam, a consultant in radiology at St George's Hospital, London, said: ‘We're being driven in a way by the licence which is probably correct, but it does have a very big difference in terms of the cost-effectiveness. We can't be driven by sub-optimal care that is already being given.'
‘Disregarding the license there is the potential that the committee would only consider the 150mg dose because it has better clinical effectiveness and is potentially more cost-effective.'
Professor Gregory Lip, professor of cardiovascular medicine at the University of Birmingham and director of the haemostasis, thrombosis and vascular biology at City Hospital Birmingham, told Pulse: ‘The message that needs to go out is that oral anticoagulation is the best therapy for stroke prevention in atrial fibrillation, whether that is by well-controlled warfarin or one of the new drugs.'
‘Bleeding risk is multi-factorial and based not just on age alone. If the 110mg dose is restricted to those aged over 80, it may deprive some patients of added benefits of 150mg.'
Dr Kathryn Griffith, chair of the Primary Care Cardiovascular Society and a GP in York with an interest in atrial fibrillation, said: ‘I think that the 110mg dose appeared as effective as warfarin [in the RELY trial] and that the over-80s have increased bleeding risk largely related to other comorbidities, so I can see that this may be sensible.'
