The European Society of Cardiology (ESC) has issued revised practice guidelines for the management of atrial fibrillation (AF), including guidance on the role of a novel oral treatment, dabigatran etexilate, for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF).

At the same time, Boehringer Ingelheim confirms that the U.S. Food and Drug Administration (FDA) granted a priority review designation for Boehringer Ingelheim’s novel oral direct thrombin inhibitor dabigatran etexilate for the prevention of stroke in AF. A priority review designation is given to new drugs that are expected to offer major advances in treatment, or provide a treatment where no adequate therapy exists. An FDA advisory committee will meet on Monday, September 20^th, to review and discuss dabigatran etexilate data.

In addition to the US, the registration process for dabigatran etexilate is underway in Europe, Japan and other countries. The company expects to receive marketing authorization for dabigatran etexilate in first countries by end of 2010 or beginning of 2011.

RE-LY^® study

All applications, including the FDA New Drug Application (NDA) are based on the results of the pivotal Phase III RE-LY^® study (Randomized Evaluation of Long-term anticoagulant therapY), published in the New England Journal of Medicine in August 2009, comparing the efficacy and safety of two doses of dabigatran etexilate with warfarin (titrated to INR¹ 2.0 to 3.0) for the prevention of stroke and systemic embolism in patients with atrial fibrillation.¹

Results from RE-LY^®, the largest AF study completed to date, showed that in patients with AF, dabigatran etexilate 150mg b.i.d. significantly reduced the risk of stroke and systemic embolism by 34% compared to warfarin, with comparable rates of major bleeding. Dabigatran etexilate 110mg b.i.d. demonstrated similar reductions in stroke and systemic embolism while delivering a reduction in major bleeding rates compared to warfarin. Additionally, both doses showed a significant reduction in haemorrhagic stroke and a significant reduction in life threatening, intracranial and total bleeding compared to warfarin.¹

Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim said, “Boehringer Ingelheim has a long term commitment to the treatment and prevention of stroke. The decision by the US FDA to grant a priority designation review is an important step in making dabigatran etexilate available for patients with atrial fibrillation to prevent them from strokes.”

New practice guidelines on atrial fibrillation

Gregory Lip, Professor of cardiovascular medicine at University of Birmingham Centre for Cardiovascular Sciences, UK and a member of the Task Force writing group for the new ESC Guidelines for the management of atrial fibrillation commented, “The updated guidelines reflect the high need for novel treatments in the prevention of atrial-fibrillation related stroke. Both the personal and economic burden of AF-related stroke is high. Consideration of new prevention therapies will improve the overall standard of care.”

Limitations of current therapy

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 ², 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 therapy³ with fewer than half of these controlled within the therapeutic INR range.⁴

Stroke is more likely to be severe and fatal in patients with AF, and those who survive face persistent neurological deficits, persistent disability and poorer functional performance.^5,6

According to Professor Jonas Oldgren, Associate Professor of Cardiology, Uppsala Clinical Research Centre (which furthermore was one of the coordinating centres in RE-LY^®), “Dabigatran etexilate is the first treatment to significantly reduce stroke in patients with atrial fibrillation across all risk groups, when compared to well-controlled warfarin. This novel direct thrombin inhibitor could represent a very important advance in the prevention of stroke in patients with AF for both healthcare professionals and patients alike.”

Dr. Oldgren referred to a sub-group analysis presented at this year’s American College of Cardiology’s annual congress in March, which assessed the rate of stroke and systemic embolism in patients defined as being at low, moderate or high risk of such events by the validated stroke risk stratification score, CHADS₂². The results of this analysis showed that dabigatran etexilate 150mg significantly reduced the number of strokes in patients with AF, irrespective of a patient’s risk profile. Dabigatran etexilate 110mg b.i.d. was associated with significantly lower major bleeding events and both dabigatran doses showed significantly lower intracranial bleeding rates when compared to well-controlled warfarin.⁷

RE-LY^® is the largest AF study ever completed (18,113 patients) investigating dabigatran etexilate vs. well controlled warfarin. RE-LY^® included patients with at least one risk factor of stroke, representative of a real-world setting. In addition, 50% of enrolled patients were naïve to previous oral anticoagulants, a population who may reflect a more realistic experience with anticoagulants, as they are more likely to represent the patient group with the highest percentages outside of the therapeutic INR range.^1,8

Up to three million people worldwide suffer strokes related to AF each year,^9-11 which tend to be especially severe and disabling,¹⁰ with half of people dying within one year.¹² Therefore, there is an clear medical need for an effective and safe anticoagulant, without the multiple limitations of VKA therapy.

To view ‘Notes to Editors’ and ‘References’, please click on the link below:

http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2010/30_august_2010_dabigatran.htm

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 U.S.A.

¹ International Normalized Ration

*CHADS₂ risk score: Congestive heart failure, hypertension: blood pressure consistently above 140/90 mmHg (or treated hypertension on medication), age >75 years, diabetes mellitus, prior stroke or TIA

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