FDA Advisory Committee Unanimously Recommends Approval of Dabigatran
Etexilate for Stroke Prevention in Atrial Fibrillation

Decision based on Canadian-led Trial from McMaster University

TORONTO, Sept. 22 /CNW/ - The U.S. Food and Drug Administration (FDA) Cardiovascular and Renal Drugs Advisory Committee on Monday voted 9 to 0 in favour of approving dabigatran etexilate for stroke prevention in patients with atrial fibrillation (AF). Atrial fibrillation, or irregular heartbeat, is a common heart condition which affects 250,000 Canadians.¹ 

Key to the FDA Advisory Committee's decision was the RE-LY^® trial; the largest randomized stroke prevention trial in AF completed to-date, with more than 18,000 patients, including 1,150 Canadians.² The study demonstrated the safety and efficacy profile of dabigatran etexilate compared to warfarin, also known as Coumadin, the current standard of care. ²

"For over two decades, we have had no choice but to use warfarin, a medication that is very challenging to work with for both physicians and patients alike," said Dr. Stuart Connolly, co-principal investigator of RE-LY^® and Director, Division of Cardiology at The Population Health Research Institute, McMaster University, Hamilton, Ontario.  "I am very pleased to see that we have a new therapy on the horizon that is more efficacious and shows impressive safety with a reduced risk of life threatening bleeding."

In its decision, the FDA Advisory Committee acknowledged the significant clinical relevance of the study results. Several committee members commented that the RE-LY^® study design was optimal because it reflects the real-life use of warfarin.

Atrial fibrillation is a serious heart condition that can lead to severe and debilitating strokes.¹ Canadians with AF have a three to five times greater risk of having a stroke and are twice as likely to die from one.¹  In Canada, stroke is the leading cause of adult disability and the third leading cause of death³ with up to 15 per cent of strokes being caused by AF. ¹

For the past 20 years, warfarin has been the only oral anticoagulant available in Canada for stroke prevention in patients with AF.⁴  It requires life-long testing, constant dose adjustments and can be affected by certain foods and medications, all of which can impact a patient's quality of life.  Of the AF patients who are eligible to receive warfarin therapy, only 51 per cent receive it and less than half of those patients are properly managed on the medication.^5,6 As a result, patients may not be properly protected from stroke.

About the RE-LY^® Trial
The RE-LY^® (Randomized Evaluation of Long term anticoagulant therapy) was a global, Phase III, randomized trial of 18,113 patients including 1,150 Canadian patients, enrolled in over 950 centres in 44 countries, including 52 centres in Canada investigating whether dabigatran etexilate (two blinded doses) was as effective as well-controlled warfarin - INR 2.0 - 3.0 - (open label) for stroke prevention.⁷ Patients with non-valvular AF and at least one other risk factor for stroke (i.e., previous ischemic stroke, transient ischemic attack, or systemic embolism, left ventricular dysfunction, ≥ 75 years, ≥ 65 with either diabetes mellitus, history of coronary artery disease, or hypertension)⁷ were enrolled in the study for two years with a minimum follow-up period of one year.⁷

The RE-LY^® trial utilized the established PROBE (prospective, randomized, open-label, blinded endpoint evaluation) clinical trial protocol, ⁷ which has been used in the majority of previous trials of anticoagulation for stroke prevention in patients with AF.⁸ A PROBE design is more reflective of the differences in the management of warfarin and dabigatran in clinical practice⁸ and it is reflective of the standard of care for patients.⁸ 

In the RE-LY^® trial, all clinical outcomes were adjudicated in a blinded manner to minimize bias in assessment of outcomes for each treatment.⁸ Gastrointestinal bleeding and dyspepsia occurred more frequently with dabigatran than with warfarin.

The RE-LY^® trial was led by Co-Chairmen Dr. Salim Yusuf, Professor of Epidemiology and Cardiology, Population Health Research Institute McMaster University, Hamilton, Canada and Dr. Lars Wallentin, Professor of Cardiology and Director of the Uppsala University, Sweden.

About atrial fibrillation and stroke
Atrial fibrillation is an irregular heart rhythm known as arrhythmia that can cause the heart to beat very fast.¹ While AF is rare in people under 40, its prevalence increases with age.¹ After the age of 55, the incidence of AF doubles with each decade of life.¹ Other risk factors include heart disease, high blood pressure and diabetes. After age 60, one-third of all strokes are caused by AF.¹ The health care costs for patients in the first six months after a stroke can total more than $2.5 billion a year.⁹  In the six-month period following a stroke, the direct and indirect health care cost for each patient is $50,000.⁹

About dabigatran etexilate
Dabigatran etexilate (Pradax™) has not been approved by Health Canada for prevention of stroke or systemic embolism in patients with atrial fibrillation.  Currently 75 mg and 110 mg capsules are available in Canada and indicated for the prevention of venous thromboembolic events in patients that have undergone elective hip replacement or knee replacement surgery.  Dabigatran etexilate is at the forefront of a new generation of oral anticoagulants - direct thrombin inhibitors (DTIs) - targeting a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases.  

About Boehringer Ingelheim (Canada) Ltd. 
The Boehringer Ingelheim group is one of the world's 15 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and 41,500 employees.

Founded in 1885, the family-owned company is committed to researching and developing novel products of high therapeutic value for human and veterinary medicine. In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro while spending one fifth of net sales in its largest business segment Prescription Medicines on research and development.

The Canadian headquarters of Boehringer Ingelheim was established in 1972 and the Research and Development Centre located in Laval, Québec, Canada since 1988. Boehringer Ingelheim (Canada) Ltd. is home to more than 700 employees including 160 scientists across the country.

For more information please visit www.boehringer-ingelheim.ca.

References
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¹ Heart and Stroke Foundation of Canada. 2009 Stroke Report Card. http://www.heartandstroke.com/site/apps/nlnet/content2.aspx?c=ikIQLcMWJtE&b=4955951&ct=708508&rc=report (Accessed September 21, 2010)

² Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Eng J Med 2009; 361:1139-1151.

³ Canadian Stroke Network.  http://www.canadianstrokenetwork.ca/index.php/about/about-stroke/stroke-101/ (Accessed September 21, 2010)

⁴ Schwartz, N, Albers, G.  Dabigatran challenges warfarin's superiority for stroke prevention in atrial fibrillation.  Stroke 2010; 41: 1307-1309.

⁵ Hylek EM, DAntonio J, Evans-Molina C, et al. Translating the results of randomized trials into clinical practice. The challenge of warfarin candidacy among hospitalized elderly patients with atrial fibrillation. Stroke 2006; 37:1075-80.

⁶ Samsa GP, Matchar DB, Goldstein LB, et al. Quality of anticoagulation management among patients with atrial fibrillation: results of a review of medical records from 2 communities. Arch Intern Med 2000; 160:967-73.

⁷ Ezekowitz 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.

⁸ Wolf PA et al. "Atrial Fibrillation as an Independent Risk Factor for Stroke: The Framingham Study." Stroke. 1991; 22:983-988.

⁹ Heart and Stroke Foundation.  http://www.heartandstroke.com/site/apps/nlnet/content2.aspx?c=ikIQLcMWJtE&b=6074245&ct=8425975 (Accessed September 21, 2010).

For further information:

Derek O'Toole    
Boehringer Ingelheim (Canada) Ltd. 
[phone]
[email protected]

Sara McClelland
Boehringer Ingelheim (Canada) Ltd.
[phone]
[email protected]