Media & PR
Dr Reinhard Malin
Binger Strasse 173
55216 Ingelheim am Rhein
Important next step for breakthrough treatment
For Media outside the US and Canada
Ingelheim, Germany, October 27, 2010 –Health Canada, the Canadian health authority, has approved PRADAX™ (dabigatran etexilate),1 Boehringer Ingelheim’s novel, oral direct thrombin inhibitor2 for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF) in whom anticoagulation is appropriate, marking the second approval of this new oral anticoagulant following the recent marketing authorisation by the US Food and Drug Administration (FDA). The Health Canada approval makes PRADAX™ available to AF patients in Canada,1 with the flexibility of two dosing regimens. While overall the 150 mg bid dose is recommended, the 110 mg bid dose is specifically available for elderly patients aged 80 years and above as well as for patients at higher risk of bleeding.
The approval is based on findings from RE-LY®, the largest AF trial completed to date and is set to provide a breakthrough for stroke prevention in AF – a condition that affects 250,000 people in Canada alone.3 The results demonstrated that dabigatran etexilate 150 mg significantly reduced the risk of stroke and systemic embolism by 35 percent beyond the reduction achieved with warfarin, the longtime standard of care, while the risk of major bleeding events was similar. Compared to well controlled warfarin, dabigatran etexilate 110 mg bid was associated with a similar reduction of stroke and systemic embolism but a lower rate of major bleeding. Importantly, both doses provided a reduction in intracranial and life-threatening bleeding, as well as in total bleeding, compared with warfarin.4 Besides providing superior efficacy compared to warfarin, dabigatran etexilate does not require monitoring or related dose adjustments, is not affected by food, and no dose adjustment is required for many common co-medications in patients with AF.
Addendum: These groundbreaking results were shown in RE-LY®, a PROBE (prospective, randomized, open-label with blinded endpoint evaluation) trial designed to compare two fixed doses of the oral direct thrombin inhibitor dabigatran (110 mg and 150 mg bid) each administered in a blinded manner, with open label warfarin.4
Besides providing superior efficacy compared to warfarin, dabigatran etexilate does not require monitoring or related dose adjustments, is not affected by food, and no dose adjustment is required for many common co-medications in patients with AF.
“Dabigatran etexilate is a significant advance in medicine. We have been waiting a long time for an alternative to warfarin. For decades, we have had no other choice than to use warfarin in the majority of patients, a treatment that imposes challenging restrictions on people’s quality of life,” said Dr. Stuart Connolly co-principal investigator of RE-LY®, Director, Division of Cardiology at McMaster University and member of The Population Health Research Institute, Hamilton, Ontario. “It is really great to finally have a safer and more effective alternative for patients with AF, which is easier to use. The approval of dabigatran etexilate will transform the way we treat and manage patients with atrial fibrillation at risk of stroke.”
Coinciding with the Health Canada approval of PRADAX™, the Canadian Cardiovascular Society (CCS) has released new guidelines on stroke prevention in atrial fibrillation, which contain guidance on the use of dabigatran etexilate. Based on the safety and efficacy profile of PRADAX™, the guidelines generally recommend its use over warfarin for overall stroke reduction, particularly the 150mg dose twice-daily.5
Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim said, “The approvals of dabigatran etexilate for stroke prevention in AF in North America are good news for patients and physicians, who now have access to a novel agent that has the potential to change the treatment paradigm in this indication. The decision of Health Canada marks another important step towards our goal to make this treatment available to all patients with atrial fibrillation at risk of stroke. We are working with regulatory authorities worldwide to ensure this.”
Notes to editors:
RE-LY® (Randomized Evaluation of Long term anticoagulant therapY) was a global, phase III, randomised trial of 18,113 patients enrolled in over 900 centres in 44 countries, investigating whether dabigatran etexilate (2 blinded doses) is as effective as well controlled warfarin with target INR of 2.0-3.0 for stroke prevention. Patients were followed-up in the study for a median of 2 years with a minimum of 1 year follow-up.
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:4
About AF and stroke
AF is the most common heart rhythm condition, affecting around 1% of the total population, rising to 10% in people over the age of 80.6 People with AF are at increased risk of blood clots, which raises stroke risk by five times.7,8 Up to three million people worldwide suffer strokes related to AF each year,9-11 which tend to be especially severe and disabling, with half of people dying within one year.12 A total of 6.3 million people in the US, Japan, Germany, Italy, France, UK and Spain were living with AF in 2007 and this is expected to increase to 7.5 million by 2017 primarily due to the ageing population.13 Strokes due to AF tend to be severe, with an increased likelihood of death (20%), and disability (60%), with resultant societal costs and burden to the healthcare system.12 AF alone is associated with a cost of up to €13.5 billion across the European Union.7
Well-controlled vitamin K antagonist (VKA) therapy (warfarin), currently used for the prevention of stroke in atrial fibrillation, is highly effective in reducing the risk of stroke by approximately two-thirds,14 but is associated with an increased risk of bleeding as well as several limitations. Drug-drug and food interactions as well as the requirement for frequent monitoring result in only about 50% of eligible patients receiving VKA therapy15 with fewer than half of these controlled within the therapeutic INR range.16
About dabigatran etexilate
Dabigatran etexilate is at the forefront of a new generation of oral anticoagulants/direct thrombin inhibitors (DTIs)2 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.
Dabigatran etexilate has already been approved in 75 countries under the trademark Pradaxa® (in Canada: Pradax®) for the primary prevention of venous thromboembolic events (blood clots) in adults who have undergone elective total hip or elective total knee replacement surgery.
Dabigatran etexilate is only approved for clinical use in stroke risk reduction in non-valvular atrial fibrillation prevention in the US and the prevention of stroke, and systemic embolism in adults with atrial fibrillation in Canada. This information is provided for medical education purposes only.
About the dabigatran etexilate clinical trial programme
Boehringer Ingelheim’s clinical trial program to evaluate the efficacy and safety of dabigatran etexilate encompasses studies in:
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 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.
In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro while spending 21% 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.
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1PRADAX Product Monograph, October 2010
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3Heart 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 July 5, 2010)
4Connolly SJ, et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009; 361:1139-51.
5Carins, John A et al. Prevention of Stroke and Systemic Embolism in Atrial Fibrillation and Flutter. Slides from the CCS Atrial Fibrillation Guidelines Symposium at CCC 2010. Chapter 5, p. 12.
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14Hart RG, Benavente O, McBride R, Pearce LA. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med 1999; 131:492-501.
15Hylek 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.
16Samsa 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.
*Dabigatran etexilate has been approved for stroke risk reduction in non-valvular atrial fibrillation as Pradaxa® in the USA.