Dabigatran Features In New AF Guidelines

The registration process for dabigatran etexilate is underway in Europe (including the UK), Japan and other countries. The manufacturer, Boehringer-Ingelheim, hopes to receive a marketing authorisation for dabigatran etexilate in first countries by end of 2010 or beginning of 2011.

RE-LY® study

All applications, including the US, 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. (2)

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 . (2)

Gregory Lip, Professor of cardiovascular medicine at University of Birmingham Centre for Cardiovascular Sciences, UK, who presented the new ESC practice guidelines for the management of AF at the ESC Congress 2010 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.”

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).

In the United Kingdom, dabigatran etexilate is NOT licensed for the prevention of stroke in patients with atrial fibrillation. Currently in the UK dabigatran can only be prescribed for the primary prevention of venous thromboembolic events in adults who have undergone elective total hip or elective total knee replacement surgery.

Dabigatran- lined up for FDA approval

A US Food and Drug Administration (FDA)  nine voting member advisory panel has recently  unanimously recommended approval of dabigatran as a potential replacement for warfarin for stroke prevention in atrial fibrillation (AF).

References

1. European Society of Cardiology committee for Practice Guidelines. Guidelines for the management of atrial fibrillation of the European Society of Cardiology. European Heart Journal August 2010.
2. Connolly SJ, et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009; 361:1139-51.