Value through Innovation24 October 2014
16 March 2012

Pradaxa® (dabigatran etexilate) – first new oral anticoagulant in nearly 60 years receives final NICE recommendation for stroke prevention in atrial fibrillation in the UK1

Ingelheim, Germany, 16 March 2011 – On 15 March, the National Institute for Health and Clinical Excellence (NICE) has issued final guidance recommending the novel oral anticoagulant, Pradaxa® (dabigatran etexilate)2 as a cost-effective option for the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (AF) and one or more risk factors.1

This landmark decision means Pradaxa® must now be made available for use by the UK National Health Service (NHS) and that patients have the right to receive it if clinicians deem it clinically appropriate.

Professor Gregory Lip, Consultant Cardiologist & Professor of Cardiovascular Medicine, University of Birmingham Centre for Cardiovascular Sciences, Birmingham, United Kingdom

Professor Gregory Lip, Consultant Cardiologist & Professor of Cardiovascular Medicine, University of Birmingham Centre for Cardiovascular Sciences, Birmingham, United Kingdom

Professor Gregory Lip, Consultant Cardiologist & Professor of Cardiovascular Medicine, University of Birmingham Centre for Cardiovascular Sciences, Birmingham, United Kingdom commented, "The final NICE recommendation of dabigatran etexilate in the UK represents a major advance in the treatment of this condition. NICE estimates that only half of eligible patients receive warfarin due to the treatment having many limitations such as the need for regular monitoring and various food-drug and drug-drug interactions. This means that many AF patients are not currently taking an anticoagulant and may therefore be at an increased risk of stroke. The approval of dabigatran etexilate has the potential to significantly reduce the risk of stroke in patients with AF who are eligible for anticoagulation therapy."

AF affects around 1% of the total population worldwide with approximately 1.2 million people diagnosed with AF in the UK alone,4 of which 77% are eligible for treatment with an anticoagulant.5 AF increases the risk of stroke by five-fold,3,6 with AF-related stroke tending to be severe and associated with a likelihood of death (20%) and disability (60%).7

Pradaxa® is now the only novel oral anticoagulant recommended for use in the UK for the prevention of stroke in AF, offering the first treatment alternative to current standard of care warfarin. This is an important landmark given that the use of Pradaxa® 150mg twice daily has the potential to prevent 470 more strokes per 100,000 patients every year compared to warfarin.8-11

The final NICE guidance of Pradaxa® for stroke prevention in AF is based on the groundbreaking results from RE-LY®, one of the largest studies ever conducted in AF including over 18,000 patients. RE-LY® was a PROBE (prospective, randomized, open-label with blinded endpoint evaluation) trial, comparing two fixed doses of the oral direct thrombin inhibitor dabigatran etexilate (110mg and 150mg bid) each administered in a blinded manner, with open label warfarin.9,10,12

Pradaxa® 150mg bid is the only novel oral anticoagulant proven superior to well-controlled warfarin (median TTR 67%12) in significantly reducing both ischaemic and haemorrhagic stroke in patients with non-valvular AF.9,10 Pradaxa® 150mg bid reduced the risk of stroke and systemic embolism by 35% while also significantly lowering the risk of life-threatening and intracranial bleeding, compared to well-controlled warfarin. 9,10 The novel treatment also does not require frequent coagulation monitoring or routine dose adjustment and has no known dietary restrictions, which can be associated with warfarin.

Pradaxa® is also approved in the UK (by NICE) for the primary prevention of venous thromboembolic events (blood clots) in adults who have undergone elective total hip or elective total knee replacement surgery.13

NOTES TO EDITORS

About AF and stroke
AF is the most common sustained heart rhythm condition,14 affecting around 1% of the total population, with one in four adults over the age of 403 developing the condition in their lifetime, rising to 10% in people over the age of 80.14 People with AF are more likely to experience blood clots, which increases the risk of stroke by five-fold.3,6 Up to three million people worldwide suffer strokes related to AF each year.15-18 Strokes due to AF tend to be severe, with an increased likelihood of death (20%), and disability (60%).7 Many AF-related strokes can be prevented with appropriate antithrombotic therapy.19 AF-related strokes currently represent a significant cost to healthcare systems across Europe. Given AF-related strokes tend to be more severe this results in direct medical costs which are higher than non AF-related strokes (€11,799 vs €8,817 P < 0.001).20

About RE-LY®
RE-LY® (Randomized Evaluation of Long term anticoagulant therapY) was a global, phase III, PROBE (prospective, randomized, open-label with blinded endpoint evaluation) trial of 18,113 patients enrolled in over 900 centres in 44 countries designed to compare two fixed doses of the oral direct thrombin inhibitor dabigatran (110mg and 150mg bid) each administered in a blinded manner, with well controlled (INR 2.0-3.0, median TTR 67%) open label warfarin.11-13 Patients were followed-up in the study for a median of 2 years with a minimum of 1 year follow-up.9,10

The primary endpoint of the trial was incidence of stroke (including haemorrhagic) or systemic embolism. Secondary outcome measures included all-cause death, incidence of stroke (including haemorrhagic), systemic embolism, pulmonary embolism, acute myocardial infarction, and vascular death (including death from bleeding).

Compared to well controlled warfarin, dabigatran etexilate showed in the trial: 9,10

  • Significant reduction in the risk of stroke and systemic embolism – including haemorrhagic strokes with dabigatran etexilate 150mg bid
  • Similar rates of stroke/systemic embolism with dabigatran etexilate 110mg bid
  • Significantly lower major bleeding events with dabigatran etexilate 110mg bid
  • Significantly lower life threatening and intracranial bleeding with both doses
  • Significant reduction in vascular mortality with dabigatran etexilate 150mg bid.

About dabigatran etexilate

Dabigatran etexilate is at the forefront of a new generation of oral anticoagulants/direct thrombin inhibitors (DTIs)21 targeting a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases.

Potent antithrombotic effects are achieved with direct thrombin inhibitors by specifically blocking the activity of thrombin (both free and clot-bound), the central enzyme in the process responsible for clot (thrombus) formation. In contrast to vitamin-K antagonists, which variably act via different coagulation factors, dabigatran etexilate provides effective, predictable and consistent anticoagulation with a low potential for drug-drug interactions and no drug-food interactions, without the need for routine coagulation monitoring or dose adjustment.

About the dabigatran etexilate clinical trial programme
Boehringer Ingelheim’s clinical trial programme to evaluate the efficacy and safety of dabigatran etexilate encompasses studies in:

  • Primary prevention of venous thromboembolism (VTE) in patients undergoing elective total hip and knee replacement surgery
  • Treatment of acute VTE
  • Secondary prevention of VTE
  • Stroke prevention in AF.

Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 42,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavors.

In 2010, Boehringer Ingelheim posted net sales of about 12.6 billion euro while spending almost 24% of net sales in its largest business segment Prescription Medicines on research and development.

Updated information on the corporation’s annual results in 2011 will be available on April 24th, 2012.

Please be advised
This release is from Boehringer Ingelheim Corporate Headquarters in Germany. Please be aware that there may be national differences between countries regarding specific medical information, including licensed uses. Please take account of this when referring to the information provided in this document. This press release is not intended for distribution within the USA or Canada.

References
1NICE final guidance, available at [insert web address] Accessed March 2012.
2Pradaxa®, Summary of Product Characteristics, 2011. Europe.
3Lloyd-Jones DM, Wang TJ, Leip EP, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation 2004; 110:1042-6.
4Atrial Fibrillation Association. February 2011. Available at http:// http://www.atrialfibrillation.org.uk/ Accessed March 2012.
5NICE Assumptions used in estimating a population benchmark http://www.nice.org.uk/usingguidance/commissioningguides/anticoagulationtherapyservice/popbench.jsp / Accessed March 2012.
6Fuster V, Rydn LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation – executive summary. Circulation 2006; 114:700-52.
7Lin HJ, Wolf PA, Kelly-Hayes M, et al. Stroke severity in atrial fibrillation: the Framingham study. Stroke 1996; 27:1760-4.
8Atrial fibrillation investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Ann Intern Med 1994; 154: 1449-57.
9Connolly SJ, et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009; 361:1139-51.
10Connolly SJ, et al. Newly identified events in the RE-LY® trial. N Engl J Med 2010;363(19): 1875-6.
11Hart RG, et al. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have non-valvular atrial fibrillation. Ann Intern Med 2007 146:857-867.
12FDA Advisory Committee Briefing Document, September 2010,http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisory Committee/UCM226009.pdf.
13NICE technology appraisal guidance. Dabigatran etexilate for the prevention of venous thromboembolism after hip or knee replacement surgery in adults. September 2008. Available at http://guidance.nice.org.uk/TA157/Guidance/pdf/English/ Accessed March 2012. 
14Stewart S, Murphy N, Walker A, et al. Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK. Heart 2004; 90:286-92.
15Kannel WB, et al. Final Draft Status of the Epidemiology of Atrial Fibrillation. Med Clin North Am. 2008; 92(1): 17–40.
16Atlas 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.
17Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991: 22(8);983-8.
18Marini C, De Santis F, Sacco S, et al. Contribution of atrial fibrillation to incidence and outcome of ischaemic stroke: results from a population-based study. Stroke 2005; 36:1115-9.
19Hart RG, Pearce LA, Aguilar MI, et al. Meta-Analysis: antithrombotic therapy to prevent stroke in patients who have non-valvular atrial fibrillation. Ann Intern Med 2007;146:857-67.
20Bruggenjurgen B et al. The Impact of Atrial Fibrillation on the Cost of Stroke: The Berlin Acute Stroke Study. Value Health 2007; 10: 137–43.
21Di Nisio M, et al. Direct Thrombin Inhibitors. N Engl J Med 2005; 353:1028-40.

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