Value through Innovation16 April 2014
26 August 2011

Pradaxa® (dabigatran etexilate) revolutionizes stroke prevention in atrial fibrillation

• More than 350,000 patients already taking Pradaxa® in the U.S., Canada and Japan less than 10 months following approval1,2,3
• Cardiologists have broadly adopted the breakthrough treatment in the U.S. and 9 out 10 that treat a majority of AF patients have prescribed it (n=14,019)4
• First trial (phase II) investigating the benefit of a novel oral anticoagulant in patients with mechanical heart valves to be initiated.

Ingelheim, Germany, 26 August 2011 – Boehringer Ingelheim today announced that more than 350,000 patients have already been prescribed Pradaxa® (dabigatran etexilate) for stroke prevention in non-valvular atrial fibrillation (AF) less than 10 months following its approval in the U.S., Canada and Japan.1,2,3 Latest data shows that cardiologists have broadly adopted the breakthrough treatment in the U.S. and 9 out 10 that treat a majority of AF patients have prescribed it (n=14,019) 4

Dabigatran etexilate was the first novel oral anticoagulant approved5-9 for stroke prevention in AF since the current standard of care warfarin was made available 55 years ago. These approvals were based on the landmark RE-LY® trial, which showed that dabigatran etexilate 150mg bid was significantly superior in reducing the risk of stroke or systemic embolism by an additional 35% compared to well-controlled warfarin10,11 (median TTR 67%4,5), while at the same time demonstrating significant reductions in intracranial and life threatening bleeds.10 The RE-LY® results were demonstrated in the intention-to-treat population, the accepted standard for reporting superiority in clinical trials.12 The RE-LY® trial was a PROBE (prospective, randomized, open-label with blinded endpoint evaluation) trial designed to compare 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.13

The broad uptake of dabigatran etexilate in stroke prevention in AF has been largely consistent across the U.S., Canada & Japan:

  • U.S.: Over 250,000 patients have been prescribed dabigatran etexilate1 – approx. 2.3 million patients are currently treated for AF in the U.S.14
  • Canada: 42,000 patients have been prescribed dabigatran etexilate2 where an estimated 250,000 patients are currently treated for AF15
  • Japan: 64,000 patients have been prescribed dabigatran etexilate following its approval in March 2011.3 An estimated 830,000 patients are currently treated for AF in the country.16
Dr. Stuart Connolly, Director, Division of Cardiology at McMaster University and member of The Population Health Research Institute, Hamilton, Ontario

Dr. Stuart Connolly, Director, Division of Cardiology at McMaster University and member of The Population Health Research Institute, Hamilton, Ontario

Dr. Stuart Connolly, Director, Division of Cardiology at McMaster University and member of The Population Health Research Institute, Hamilton, Ontario said, "The large number of patients using dabigatran etexilate is great news and not surprising, given that the treatment is a superior and more convenient alternative to warfarin in stroke prevention in AF. The experience that physicians are gaining in using dabigatran etexilate in clinical practice is invaluable, and I hope this is shared and utilized to lead to more patients using this novel treatment worldwide."

In Canada and the U.S., the majority of physicians consider the performance of dabigatran etexilate to be better than warfarin on all relevant attributes in clinical practice,17,18 with Canadian physicians prefering the novel treatment mainly due to its superior stroke prevention and the fact that it does not require routine monitoring.17 In addition, physicians in the U.S. have been using the novel treatment in a broad range of patients, with 30% of prescriptions written for patients over the age of 80.19

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

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

Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim said, "We are proud that dabigatran etexilate, a drug from our own research and development, is being used worldwide to help protect patients from the potentially devastating effects of an AF-related stroke. Our commitment in this area is resolute, and with the extensive RE-VOLUTION® clinical trial programme evaluating the efficacy and safety of dabigatran etexilate in over 40,000 patients in six different potential indications, Boehringer Ingelheim is at the forefront to make new anticoagulant treatment options available to patients."

Boehringer Ingelheim is now underlining its leadership position with the initiation of the first trial (phase II) investigating the potential benefit of a novel oral anticoagulant in patients with mechanical heart valves. The RE-ALIGN trial (Randomised, phase II study to Evaluate the sAfety and pharmacokinetics of oraL dabIGatran etexilate in patients after heart valve replacement) will evaluate the dosages of dabigatran etexilate of150mg to 300mg bid in a potential future indication, an area of growing medical need and prevalence, given that the number of heart valve implants is expected to triple to 850,000 by 2050 due to the aging population.20

Prof. Frans Van de Werf, Department of Cardiovascular Medicine, University Hospitals Leuven, Belgium

Prof. Frans Van de Werf, Department of Cardiovascular Medicine, University Hospitals Leuven, Belgium

Prof. Frans Van de Werf, Department of Cardiovascular Medicine, University Hospitals Leuven, Belgium said, "The only effective option currently available for patients who undergo mechanical heart valve replacement to prevent valve thrombosis and thromboembolism are vitamin K antagonists, which have many limitations in clinical practice. The RE-ALIGN trial will provide us with important first insights into the potential use of dabigatran etexilate in this area. It is important to note that dosages tested in this study include ones that are significantly higher than those currently approved for use in stroke prevention in AF."

NOTES TO EDITORS

About AF and stroke
AF is the most common sustained heart rhythm condition,21 with one in four adults over the age of 4022 developing the condition in their lifetime. People with AF are more likely to experience blood clots, which increases the risk of stroke by five-fold.22,23 Up to three million people worldwide suffer strokes related to AF each year.24-27 Strokes due to AF tend to be severe, with an increased likelihood of death (20%), and disability (60%).28 Many AF-related strokes can be prevented with appropriate antithrombotic therapy.29 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 patient costs which are higher than non AF-related strokes annually (€11,799 vs €8,817 P < 0.001).30

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.5,6,10,11 Patients were followed-up in the study for a median of 2 years with a minimum of 1 year follow-up.10,11

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: 10,11

  • 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)31 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
  • Prevention of thromboembolism after heart valve replacement.

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.

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
1Data on file. Boehringer Ingelheim Pharmaceuticals U.S., Inc.
2Data on file. Boehringer Ingelheim Pharmaceuticals Canada, Inc.
3Data on file. Boehringer Ingelheim Pharmaceuticals Japan, Inc.
4Data on file. Boehringer Ingelheim Pharmaceuticals U.S., Inc.
5.Pradaxa®, Summary of Product Characteristics, August 2011. Europe.
6U.S. Food and Drug Administration – Pradaxa® Prescribing Information.Oct 19th, 2010.
7Health Canada – PRADAX™ Product Monograph. Oct 26th, 2010.
8Prazaxa® product information, January 2011, Japan.
9Pradaxa®, Australian Product information, April, 2011.
10Connolly SJ, et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009; 361:1139-51.
11Connolly SJ, Ezekowitz MD, Yusuf S, Reilly PA, Wallentin L: Newly identified events in the RE-LY® trial. N Engl J Med 2010; 363(19): 1875-1876.
12Piaggio G, et al. Reporting of non-inferiority and equivalence randomized trials. An extension of the CONSORT statement. JAMA. 2006; 295:1152-1160.
13Ezekowitz MD, et al. Rationale and Design of RE-LY®: Randomized Evaluation of Long-Term Anticoagulation Therapy, Warfarin, Compared with Dabigatran. American Heart Journal 2009; 157:805-810.
14Go, A.S., et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors In Atrial Fibrillation (ATRIA) Study. JAMA 2001; 285(18): 2370-2375.
15Heart and Stroke Foundation of Canada. 2009 Stroke Report Card. http://www.heartandstroke.on.ca/site/c.pvI3IeNWJwE/b.5232131/k.E66/2009_Stroke_Report_Card__full_report.htm (Accessed 16 August 2011)
16Inoue H, et al. Prevalence of atrial fibrillation in the general population of Japan: An analysis based on periodic health examination. International Journal of Cardiology 2009; 137:102–107
17Data on file. Boehringer Ingelheim Pharmaceuticals Canada, Inc.
18Data on file. Boehringer Ingelheim Pharmaceuticals U.S., Inc.
19Data on file. Boehringer Ingelheim Pharmaceuticals U.S., Inc.
20Sun J CJ, et al. Antithrombotic management of patients with prosthetic heart valves: current evidence and future trends. Lancet 2009; 374:565–76.
21tewart 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.
22Lloyd-Jones DM, Wang TJ, Leip EP, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation 2004; 110:1042-6.
23Fuster 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.
24Kannel WB, et al. Final Draft Status of the Epidemiology of Atrial Fibrillation. Med Clin North Am. 2008; 92(1): 17–40.
25Atlas of Heart Disease and Stroke, World Health Organization, September 2004. Viewed Dec 2010 at www.who.int/cardiovascular_diseases/en/cvd_atlas_15_burden_stroke.pdf .
26Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991: 22(8);983-8.
27Marini 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.
28Lin HJ, Wolf PA, Kelly-Hayes M, et al. Stroke severity in atrial fibrillation: the Framingham study. Stroke 1996; 27:1760-4.
29Hart 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.
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31Di Nisio M, et al. Direct Thrombin Inhibitors. N Engl J Med 2005; 353:1028-40.

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