New data from the RELY-ABLE study have provided additional support to the safety profile and efficacy of Pradaxa(R) (dabigatran etexilate) for stroke prevention in patients with nonvalvular atrial fibrillation (AF) over a period in excess of 2 years.[*][1]

The new long-term results presented at the American Heart Association's (AHA) Scientific Sessions, are consistent with the findings from the RE-LY trial[*]. The rates of stroke and haemorrhage observed during an additional 2.3 years of blinded follow-up in RELY-ABLE correspond to the initial RE-LY results, with the benefit of both doses of dabigatran etexilate sustained throughout the study's duration.[1]-[3] 

 The combined data from RE-LY and RELY-ABLE provides over four years of clinical trial experience and constitutes the longest evaluation of the benefits and safety of any novel oral anticoagulant for stroke prevention in AF to date. The international multi-center RELY-ABLE study followed 5,851 patients on dabigatran etexilate for a further 28 months after completion of the RE-LY trial. It examined the long-term benefits of the two treatment doses (110mg bid and 150mg bid) in an ongoing randomised and blinded approach. 

 The results from RELY-ABLE support sustained dose benefits in the long-term use of dabigatran etexilate:[1] 

- Rates of ischaemic stroke 1.15%/year on 150mg bid and 1.24%/year on 110mg bid

- Incidence of haemorrhagic stroke 0.13%/year on 150mg bid and 0.14%/year on 110mg bid

- Incidence of major bleeding 3.74%/year on 150mg bid and 2.99%/year on 110mg bid

 The consistent incidences of ischaemic and haemorrhagic stroke as well as rates of intracranial bleeding observed indicate that dabigatran etexilate provides sustained benefits. Furthermore, both doses of dabigatran etexilate had a similar net clinical benefit and mortality rates. The safety profile of dabigatran etexilate was consistent with the findings from the RE-LY trial. 

 "Most patients with atrial fibrillation need life-long anticoagulant treatment to reduce the risk of ischaemic stroke. The long-term data we now have for dabigatran etexilate are reassuring for both patients and physicians," said RELY-ABLE lead investigator Professor Stuart Connolly, Director of the Division of Cardiology at McMaster University, Hamilton, Ontario. "RELY-ABLE shows that the results seen in RE-LY continue to be observed during longer-term follow up. We see similar rates of stroke and systemic embolism and similar rates of major bleeding with similar rates of intracerebral bleeding and intracranial haemorrhage." 

 "The results from RELY-ABLE will be a valuable contribution to evidence-based decision-making in the selection of a treatment that is effective in patients with AF over the longer term," said Professor Gregory Lip, Professor of Cardiovascular Medicine at the University of Birmingham, UK. "Despite the prevalence of AF and the associated five-fold increase in risk of stroke, there remains significant scope for improvement in reducing the risk of stroke in the AF patient population. RELY-ABLE will serve to give added confidence to physicians in the appropriate prescribing of dabigatran etexilate." 

"We remain committed to the ongoing investigation of dabigatran etexilate in reducing the risk of stroke in patients living with AF," said Charles de Wet, Medical Director at Boehringer Ingelheim. "Providing further data of dabigatran's positive net benefits in clinical settings may support physicians in their prescribing decisions in managing this increasingly prevalent condition over the long term."

 In March 2012, the National Institute for Health and Clinical Excellence (NICE) issued final guidance recommending dabigatran etexilate[4] as a cost-effective option for the prevention of stroke and systemic embolism in adult patients with nonvalvular AF and one or more risk factors.[5] This decision from NICE means dabigatran must be made available for use by the NHS and that patients have the right to receive it if clinicians deem it clinically appropriate.

AF is the most common heart rhythm condition in the UK,[6] affecting more than 1.2 million people[7] and is a leading cause of stroke.[8] Approximately 150,000 people have a stroke in the UK[9] each year, of which an estimated 15% are caused by AF.[10]Lifetime risks for development of AF are 1 in 4 for both men and women 40 years of age and older.[11] The prevalence of AF rises to 10% in people over the age of 80.[6],[12] People with AF are at a five-fold increased risk of suffering a stroke, compared to those without AF.[13],[14]

Over two million people worldwide suffer strokes related to AF each year.[15],[16] Strokes due to AF are more severe with an increased likelihood of death and disability compared to non-AF stroke.[14] The mortality rate of patients with AF is about double that of patients in normal sinus rhythm.[12] Ischaemic strokes are the most common type of AF-related stroke, accounting for 92% of strokes experienced by AF patients and frequently leading to severe debilitation.[17]-[21] Many AF related strokes can be prevented with appropriate antithrombotic therapy.[22]

It is estimated that stroke care costs the NHS GBP2.8 billion in direct care costs, and costs the wider economy an additional GBP1.8 billion in loss of productivity and disability.[23]

In the UK, the average cost of AF-related stroke per patient is over GBP10,000 which can increase by up to a further GBP8,000 per year in follow-up costs if the stroke is disabling.[24]

*. Randomized Comparison of the Effects of Two Doses of Dabigatran Etexilate on Clinical Outcomes Over 4.3 Years: Results of the RELY-ABLE Double-blind Randomized Trial. Lead author: Stuart J Connolly. CS.04. Clinical Science: Special Reports: Valvular Heart Disease, PAD, Atrial Fibrillation: International Perspectives

†. RE-LY® was a PROBE trial (prospective, randomized, open-label with blinded endpoint evaluation), comparing two fixed doses of the oral direct thrombin inhibitor dabigatran etexilate (110mg bid and 150mg bid) each administered in a blinded manner, with open label warfarin.

References:

  1. Connolly SJ, et al. Randomized Comparison of the Effects of Two Doses of Dabigatran Etexilate on Clinical Outcomes Over 4.3 Years: Results of the RELY-ABLE Double-blind Randomized Trial. CS.04. Clinical Science: Special Reports: Valvular Heart Disease, PAD, Atrial Fibrillation: International Perspectives. Presented on 7 November 2012 at the American Heart Association Scientific Sessions 2012.
  2. Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-51.
  3. Connolly SJ, et al. Newly identified events in the RE-LY trial. N Engl J Med. 2010;363:1875-6.
  4. NICE final guidance, available at: http://guidance.nice.org.uk/TA249/Guidance/pdf/English Accessed November 2012  
  5. Pradaxa 150mg SPC, available at: http://www.medicines.org.uk/emc/medicine/24839 Accessed November 2012  
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  9. The Stroke Association: About Stroke, available at: http://www.stroke.org.uk/about-stroke  Accessed November 2012
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  24.  Luengo-Fernandez R, Yiin G, Gray AM&Rothwell PM. Population-based study of acute and long-term health and social care costs after stroke in patients with AF. BI data on file DBG11-03. Submitted to Stroke March 2011.
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