Boehringer Ingelheim
Media & PR
Dr Reinhard Malin
Binger Strasse 173
55216 Ingelheim am Rhein
GERMANY
Value through Innovation17 January 2013
08 November 2010
Dabigatran etexilate demonstrates substantial clinical benefits in atrial fibrillation patients with prior stroke or transient ischaemic attack
For Media outside the US
Ingelheim, Germany, 8 November, 2010. Today, The Lancet Neurology published positive results from a sub-group analysis of the landmark Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY®) trial - the largest atrial fibrillation (AF) outcomes trial ever completed (18,113 patients in 44 countries worldwide). The new findings fully support the convincing results from the
RE-LY® trial and show that AF patients with previous stroke or transient ischemic attack (TIA) may benefit substantially from treatment with dabigatran etexilate.1,2,3
The new sub-group analysis from RE-LY® included 3,623 AF patients who had suffered a stroke or TIA before enrolment into the trial. The results of the sub-group analysis were consistent with the overall trial results for the major efficacy and safety outcomes. This was confirmed by an interaction analysis which showed that results in patients with previous stroke or TIA were consistent with the overall results found in the RE-LY® trial.1,2,3
The 150 mg dose of dabigatran etexilate provided a substantial 25% reduction in relative risk compared with well controlled warfarin in the combined endpoint of stroke and systemic embolism in the sub-group of patients with previous stroke or TIA in line with the results of the main RE-LY® trial. However, due to the five fold smaller sample size of this subpopulation compared to RE-LY®, this difference did not reach statistical significance. Impressively, both doses (110 mg BID and 150 mg BID) also demonstrated significant reductions in intracranial bleeds versus well controlled warfarin.1 These findings support the overall striking results of RE-LY® in the prevention of stroke and systemic embolism of dabigatran etexilate,2,3 within a patient sub-group who are at 2.5 times increased risk compared with a typical AF patient without previous stroke or TIA, who themselves are already at 5-times increased risk.4,5,6
Addendum: RE-LY® 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 (110mg and 150mg bid) each administered in a blinded manner, with open label warfarin. Pradaxa® 110 mg bid was shown to be as effective as warfarin. Both doses of Pradaxa® showed significantly lower intracranial bleeding compared to well-controlled warfarin.2,3
Based on the convincing results of RE-LY®, dabigatran etexilate was approved in the USA for stroke risk reduction in patients with non-valvular AF and in Canada for the prevention of stroke and systemic embolism in patients with AF for whom anticoagulation is appropriate.7,8
New data from the RE-LY® trial and dabigatran etexilate will be available at this year’s American Heart Association Scientific Sessions 2010, Chicago, U.S, 13-17 November.
- ENDS -
Notes to editors:
About RE-LY®
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:2,3
- Significant reduction in the risk of stroke and systemic embolism – including haemorrhagic strokes with dabigatran etexilate 150 mg bid
- Significantly lower major bleeding events with dabigatran etexilate 110 mg bid
- Significantly lower life threatening and intracranial bleeding with both doses
- Significant reduction in vascular mortality with dabigatran etexilate 150 mg bid.
- Addendum: RE-LY® 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 (110 mg and 150 mg bid) each administered in a blinded manner, with open label warfarin.
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 80.9 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,10-13 which tend to be especially severe and disabling, with half of people dying within one year.13A 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.14 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.13 AF alone is associated with a cost of up to €13.5 billion across the European Union.4
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,15 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 therapy16 with fewer than half of these controlled within the therapeutic INR range.17
About dabigatran etexilate
Dabigatran etexilate is at the forefront of a new generation of oral anticoagulants/direct thrombin inhibitors (DTIs)18 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.
Disclaimer
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:
Primary prevention of venous thromboembolism (VTE) in patients undergoing elective total hip and knee replacement surgeries
- Treatment of acute VTE
- Secondary prevention of VTE
- Secondary prevention of cardiac events in patients with acute coronary syndrome (ACS)
- Stroke prevention in atrial fibrillation (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 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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References
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4. Fuster 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.
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7. U.S. Food and Drug Administration – Pradaxa® Prescribing Information. Oct 19th, 2010.
8. Health Canada – PRADAX™ Prescribing Information. Oct 26th, 2010.
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