NPC Archive Item: Dabigatran etexilate▼ has benefits over warfarin in patients with atrial fibrillation, but long-term evidence on efficacy and safety is required

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23 November 2010

An editorial in the British Medical Journal discusses the role of dabigatran etexilate in patients with atrial fibrillation (AF) and concludes that it has some benefits but evidence on long-term efficacy and safety is lacking.

Dabigatran etexilate is currently in licensing for prevention of stroke in patients with AF.  Should this indication be approved, then the number of eligible patients could be large. Decision-makers are advised to engage with stakeholders to:-

  • identify those patients for whom the drug might be appropriate
  • plan for and assess the implications of changes to anticoagulation services
  • take into account NICE guidance anticipated in June 2011. 

Patients with AF are known to be at increased risk of stroke. AF affects about 1.2% of the population with prevalence increasing with age. NICE guidance for the management of patients with AF recommends thromboprophylaxis with either warfarin or aspirin depending on their level of risk, and after consideration of individual patient factors. Dose-adjusted warfarin is the most effective and preferred option for people who are at high risk of stroke. However, it is associated with a higher bleeding risk than aspirin, and is not recommended for those at low risk of stroke.

Dabigatran etexilate is a prodrug that directly inhibits thrombin. It was recently approved by the FDA to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation, and is in licensing in Europe.

A recent BMJ editorial discusses the data from the RE-LY study involving 18,113 patients with AF and at least one other risk factor for stroke.  We have reviewed this study previously.

The editorial notes that the RE-LY trial was conducted in a select group of patients and the outcomes may be difficult to extrapolate to everyday clinical practice. The clinical benefits in reducing stroke and systemic emboli have to be balanced against an excess of dyspepsia, gastrointestinal bleeding, myocardial infarction and the potential to accumulate in patients suffering from renal dysfunction. The authors highlight the groups of patients for whom they consider the drug may be appropriate.

The long-term effects of dabigatran etexilate, beyond the average two year duration of follow-up in RE-LY, are also unknown but are being evaluated in an ongoing follow-up study (RELY-ABLE) of patients enrolled in RE-LY.

As we discussed previously dabigatran etexilate, unlike warfarin, does not require regular anticoagulant monitoring, and there might be an opportunity to reduce some costs associated with anticoagulation services and reduce the impact of the monitoring component on patient’s lives. Whilst the cost/daily dose of dabigatran etexilate is likely to be lower than for its orthopaedic indication, it will be higher than that for warfarin. Commissioners may wish to include in their planning that many of the costs associated with current warfarin services will be fixed, due to the need to maintain the existing infrastructure for long-standing patients whilst the place in therapy of newer antithrombotics is established.

A NICE appraisal of dabigatran etexilate for the management of patients with AF is underway and due to be published in June 2011. Commissioners are advised to agree a protocol with local stakeholders for the use of the drug and to plan ahead for the NICE guidance.

For more information on the background and treatment options for AF, including the evidence supporting the use of warfarin and aspirin, please refer to the atrial fibrillation section of NPC.

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