RELY-ABLE®: Unprecedented Long-term Data Support Safety Profile and Sustained Efficacy of Pradaxa® for Stroke Prevention in AF

• Presented at AHA’s Scientific Sessions 2012, first long-term results from RELY-ABLE® study demonstrate that advantages of Pradaxa® (dabigatran etexilate) treatment are maintained over more than 4 years
• Pradaxa® is the first and only novel oral anticoagulant supported by long-term clinical data
• Sustained benefits for both doses allow for persistent brain protection and tailored treatment according to patient needs

Los Angeles, CA, 8 November, 2012 – Pivotal data from the RELY-ABLE® study have provided additional data to support the long-term safety profile and efficacy of Pradaxa® (dabigatran etexilate) for stroke prevention in patients with non-valvular atrial fibrillation (AF).*<1> The new long-term results presented at the American Heart  Association’s (AHA) Scientific Sessions, are highly consistent with the findings from the landmark RE-LY® trial**, based upon which the treatment was approved in countries all over the world. The rates of stroke and  haemorrhage observed during the 2.3 years of blinded follow-up in RELY-ABLE® correspond to the initial RE-LY® results, supporting the benefit of both doses of Pradaxa® for tailored brain protection.<1-3>
The combined data from RE-LY® and RELY-ABLE® equates to over four years of experience and provides the most comprehensive evaluation of the benefits and safety of any novel oral anticoagulant for stroke prevention in AF to date.

 



Professor Stuart Connolly, Director of the Division of Cardiology at McMaster University, Hamilton, Ontario


“Most patients with atrial fibrillation need life-long anticoagulant treatment to be protected from ischaemic stroke. The unique 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 long-term follow up. We see the similar rates of stroke or systemic embolism and the similar rates of major bleeding with similar rates of intracerebral bleeding and intracranial haemorrhage.”
The international multi-centre RELY-ABLE® study followed 5,851 patients on Pradaxa® 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 comparison.
The results from RELY-ABLE® support sustained dose benefits in the long-term use of Pradaxa®:<1>
 

• Rates of ischemic stroke 1.15%/year on 150mg bid and 1.24%/year on 110mg bid
• Incidence of hemorrhagic stroke 0.13%/year on the 150mg bid and 0.14%/year on 110mg bid
• Incidence of major bleeding 3.74%/year on 150 mg bid and 2.99%/year on 110 mg bid
• Rates of intracranial bleeding 0.33 %/year on the DE 150mg bid and 0.25%/year on DE 110mg bid

The consistent incidences of ischaemic and haemorrhagic stroke as well as rates of intracranial bleeding observed indicate that Pradaxa® provides ongoing protection to the brain. Furthermore, both doses of Pradaxa® had similar net clinical benefit and mortality rates. The safety profile of Pradaxa® was consistent with the findings from the RE-LY® trial.





Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim


“The results from the RELY-ABLE® study are consistent with the excellent results we have seen in the RE-LY® trial and strongly support the long-term safety profile and  efficacy of Pradaxa® for stroke prevention in atrial fibrillation,” stated Professor Klaus Dugi, Corporate Senior Vice President   Medicine, Boehringer Ingelheim. “Physicians can be confident in the sustained brain protection and treatment advantages offered by both doses of Pradaxa®, and can tailor their treatment according to patient needs, as these first long-term clinical data for a novel oral anticoagulant show.”
Pradaxa® 150mg bid is the only novel oral anticoagulant, study of which has shown a significant reduction in the incidence of ischaemic strokes in patients with non-   valvular AF compared to warfarin, offering a relative risk reduction of 25%.<2> Nine out of ten strokes caused by AF are ischemic strokes,4 which can result in irreversible neurological injury with profound long-term consequences such as paralysis or    inability to move one’s limbs or formulate speech.<5>
Furthermore in RE-LY®, Pradaxa® 150mg bid provided a 35% reduction in the overall risk of stroke and systemic embolism versus warfarin (INR 2-3, median TTR 67%6). Pradaxa® 110mg bid, which is indicated for certain patients, was shown to be non-inferior compared to warfarin for the prevention of stroke and systemic embolism. Both doses of Pradaxa® were associated with significantly lower total, intracranial and life-threatening bleeding compared to warfarin. Pradaxa 150mg showed a similar risk of major bleeds versus warfarin and Pradaxa® 110mg bid additionally demonstrated significantly lower major bleeding.<2>
Clinical experience of Pradaxa® in all licensed indications is well established and continues to grow, equating to over one million patient-years in all licensed indications in over 70 countries worldwide <7> and exceeding that of all other novel oral anticoagulants.<8> 

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> Hannon, N., et al. “Stroke Associated with Atrial Fibrillation – Incidence  and Early Outcomes in the North Dublin Population Stroke Study.” Cerebrovascular Diseases. 2010;29:43-49.
^<5> NHLBI website. “What is Stroke?” Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/stroke. Accessed on: October 10, 2012.
^<6> Pradaxa European Summary of Product Characteristics, 2012
^<7> Boehringer Ingelheim data on file.
^<8> Eikelboom JW. et al. Does dabigatran improve stroke-prevention in atrial fibrillation? Reply to a rebuttal. J Thromb Haemost. 2010;8:1438–9.
^<9> Stewart S, et al. Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK. Heart. 2004;90:286-92.
^<10> Lloyd-Jones DM, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004;110:1042-6.
^<11> Fuster V, et al. ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation – executive summary. Circulation. 2006;114:700-52.
^<12> Global Atlas on Cardiovascular Disease Prevention and Control, World Health Organization in collaboration with the World Heart Federation and the World Stroke Organization 2011. Viewed May 2012 at http://www.world-heart-federation.org/fileadmin/user_upload/documents/Publications/Global_CVD_Atlas.pdf.
^<13> Atlas of Heart Disease and Stroke, World Health Organization, September 2004. Viewed Dec 2010 at http://www.who.int/cardiovascular_diseases/en/cvd_atlas_15_burden_stroke.pdf.
^<14> Wolf PA, et al. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22:983-8.
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^<17> Paolucci S, et al. Functional outcome of ischemic and hemorrhagic stroke patients after inpatient rehabilitation. Stroke. 2003;34:2861−5.
^<18> Petrea RE, et al. Gender differences in stroke incidence and poststroke disability in the Framingham Heart Study. Stroke. 2009;40:1032-7.
^<19> Meschia JF, et al. Genetic susceptibility to ischemic stroke. Nat Rev Neurol. 2011;7:369−78.
^<20> Andersen KK, et al. Hemorrhagic and ischemic strokes compared: stroke severity, mortality, and risk factors. Stroke. 2009;40:2068−72.
^<21> Roger VL, et al. AHA Statistical Update. Heart Disease and Stroke Statistics—2011 Update. A Report From the American Heart Association. Circulation 2011; 123:e18−e209.
^<22> Hart RG, et al. Meta-analysis: Antithrombotic Therapy to Prevent Stroke in Patients Who Have Nonvalvular Atrial Fibrillation Ann Intern Med. 2007;146:857-67.
^<23> Coyne KS, et al. Assessing the direct costs of treating nonvalvular atrial fibrillation in the United States. Value Health 2006; 9:348-56.
^<24> Ringborg A, et al. Costs of atrial fibrillation in five European countries: results from the Euro Heart Survey on atrial fibrillation. Europace 2008; 10:403-11.
^<25> Brüggenjürgen B, et al. The impact of atrial fibrillation on the cost of stroke: the Berlin acute stroke study. Value Health 2007;10:137-43.
^<26> Di Nisio M, et al. Direct thrombin inhibitors. N Engl J Med 2005; 353:1028-40.

*  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 (110 mg bid and 150 mg bid) each administered in a blinded manner, with open label warfarin.

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