New Pradaxa® clinical study to explore practical management of patients with atrial fibrillation undergoing ablation

• Annually more than 200,000 atrial fibrillation (AF) patients undergo ablation globally, a procedure to normalise their heart rhythm1,2,3
• Blood thinning treatments that prevent stroke and blood clots are crucial during ablation, as the procedure increases risk of blood clots4
• New RE-CIRCUITTM trial will assess the safety and efficacy of uninterrupted treatment with the blood thinner Pradaxa® during ablation5

For media outside of the U.S., the UK & Canada only

Ingelheim, Germany, 20 June, 2014 – Boehringer Ingelheim today announces a new study of Pradaxa® (dabigatran etexilate) in patients with atrial fibrillation (AF). The RE-CIRCUIT™ study will investigate the safety and efficacy of uninterrupted anticoagulant treatment with Pradaxa® in patients with AF who undergo ablation.5 Results of the study are expected in 2016.

Ablation is a routine, minimally-invasive procedure which is conducted to normalise the heart rhythm.6 Every year more than 200,000 ablation procedures are conducted globally in patients with AF who suffer from an irregular heart rhythm.1,2,3 For most patients with AF, taking an anticoagulant is essential because their irregular heart beat increases their risk of stroke by up to five times.7 Preventing blood clots and stroke is even more important during ablation because the procedure itself temporarily increases the risk of blood clots for patients.4

“Currently there are no international guidelines regarding the specific use of novel oral anticoagulants (NOACs) during ablation procedures, despite their wide use in patients with atrial fibrillation. This study will provide valuable insights with regard to the practical management of patients requiring anticoagulation during these procedures,” commented Professor Hugh Calkins, Chairman of the RE-CIRCUIT™ Study Steering Committee and Professor of Cardiology and Director of the Electrophysiology Laboratory and Arrhythmia Service, Johns Hopkins Hospital, Baltimore, USA. “We believe that dabigatran may provide a beneficial alternative to standard anticoagulation with warfarin during ablation procedures. The possibility to provide continuous anticoagulation with dabigatran during ablation would simplify management for physicians.”

RE-CIRCUIT™ is one of a number of new studies currently being initiated by Boehringer Ingelheim within the RE-VOLUTION® clinical trial programme, to further research of Pradaxa® in different clinical situations and new patient populations.5 The extensive RE-VOLUTION® clinical trial programme for Pradaxa®, which also encompasses the recently announced RE-DUAL PCI™ and RE-SPECT ESUS™ studies, will include 15 clinical trials involving over 55,000 patients in more than 44 countries globally when the new trials are completed.5

Pradaxa® is currently approved in over 100 countries worldwide and is the only novel oral anticoagulant with more than 6 years of long-term data.5 The key indication for Pradaxa® is the prevention of stroke and systemic embolism in adult patients with non-valvular AF, for which current guidelines have issued Class I recommendations for use of Pradaxa®.8,9,10 Clinical experience of Pradaxa® equates to over 3 million patient-years in all licensed indications.5

NOTES TO THE EDITORS

About RE-CIRCUIT™
The RE-CIRCUIT™ study (Randomized Evaluation of dabigatran etexilate Compared to warfarIn in pulmonaRy vein ablation: assessment of different peri-proCedUral antIcoagulation sTrategies) will explore the use of uninterrupted Pradaxa® therapy during ablation compared to uninterrupted warfarin. RE-CIRCUIT™ is an international study and will include 610 patients with either paroxysmal or permanent AF, who are scheduled to undergo a first ablation procedure.5 Treatment will be equally and randomly split between the patients taking Pradaxa® 150mg twice daily or warfarin at an international normalised ratio of 2.0 to 3.0.5 Patients will be followed-up for 90 days following their procedure.5

The primary measure of successful treatment in the RE-CIRCUIT™ clinical trial is the frequency of major bleeding, as defined by the International Society on Thrombosis and Haemostasis (ISTH),11 at 90 days after the ablation procedure. Secondary measures include the frequency of stroke or blood clots in the first 30 days and then at 90 days after the procedure; ISTH major bleeding 30 days after the procedure; and the net clinical benefit (the combined frequency of ISTH major bleeding events and blood clots or stroke) at day 30 and day 90 after the procedure as well as those complications related initially to the ablation procedure (pericardial tamponade or vascular access complications).5​

About Pradaxa® (dabigatran etexilate)
Clinical experience of Pradaxa® (dabigatran etexilate) exceeds that of all other novel oral anticoagulants, equating to over 3 million patient-years in all licensed indications worldwide. Pradaxa® has been in the market for more than 6 years and is approved in over 100 countries.5​

Currently approved indications for Pradaxa® are:12,13​

  • Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and a risk factor for stroke
  • Primary prevention of venous thromboembolic events in patients undergoing elective total hip replacement surgery or total knee replacement surgery
  • Treatment of DVT and PE and the prevention of recurrent DVT and PE in adults

Pradaxa®, a direct thrombin inhibitor (DTI), was the first widely approved drug in a new generation of direct oral anticoagulants, available to target a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases.12,14 Potent antithrombotic effects are achieved with direct thrombin inhibitors by specifically blocking the activity of thrombin, the central enzyme in the process responsible for clot (thrombus) formation.15 In contrast to vitamin-K antagonists, which variably act via different coagulation factors, Pradaxa® provides effective, predictable and reproducible anticoagulation with a low potential for drug-drug interactions and no drug-food interactions, without the need for routine coagulation monitoring or mandatory dose adjustment.14,16

Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, Boehringer Ingelheim operates globally with 142 affiliates and a total of more than 47,400 employees. The focus of the family-owned company, founded in 1885, is researching, developing, manufacturing and marketing new medications of high therapeutic value for human and veterinary medicine.

Taking social responsibility is an important element of the corporate culture at Boehringer Ingelheim. This includes worldwide involvement in social projects, such as the initiative "Making more Health" and caring for the employees. Respect, equal opportunities and reconciling career and family form the foundation of the mutual cooperation. In everything it does, the company focuses on environmental protection and sustainability.

In 2013, Boehringer Ingelheim achieved net sales of about 14.1 billion euros. R&D expenditure corresponds to 19.5% of its net sales.

Referências

  1. Auricchio A, et al. The Current Status of Cardiac Electrophysiology in ESC Member Countries. The EHRA White Book 2013. Available at: http://www.escardio.org/communities/EHRA/publications/Documents/ehra-white-book-2013.pdf. Last accessed June 2014.
  2. JRCAC Data Center 2013.
  3. O’Connor E, Minihan D. Cardium Study: Atrial Fibrillation, Decision Resources, February 2013.
  4. Calkins H, et al. 2012 HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: Recommendations for Patient Selection, Procedural Techniques, Patient Management and Follow-up, Definitions, Endpoints, and Research Trial Design. Europace 2012;14:528-606.
  5. Boehringer Ingelheim Data on File.
  6. Catheter Ablation. Available at: http://www.heartrhythmcharity.org.uk/www/203/0/Catheter_ablation_/. Last accessed June 2014.
  7. Camm AJ, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation. Eur Heart J. 2012;33(21):2719-47.
  8. De Caterina R, et al. 2012 Focused update of the ESC Guidelinesfor the management of atrial fibrillation, European Heart Journal (2012) 33:2719–2747.
  9. January C, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive Summary, J Am Coll Cardiol. 2014. Available at: http://content.onlinejacc.org/article.aspx?articleid=1854230. Last accessed: June 2014.
  10. Kernan WN, et al. AHA/ASA Guideline: Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association, Stroke. 2014. Available at: http://stroke.ahajournals.org/content/early/2014/04/30/STR.0000000000000024.abstract. Last accessed: June 2014.
  11. Schulman S, et al. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost. 2009; 8: 202-4.
  12. Pradaxa® European Summary of Product Characteristics, 2014.
  13. PRADAXA Prescribing Information, 2014. Available at: http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf.  Last accessed: June 2014.
  14. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–95.
  15. Di Nisio M, et al. Direct thrombin inhibitors. N Engl J Med. 2005;353:1028–40.
  16. Stangier J, et al. Pharmacokinetic Profile of the Oral Direct Thrombin Inhibitor Dabigatran Etexilate in Healthy Volunteers and Patients Undergoing Total Hip Replacement. J Clin Pharmacol. 2005;45:555–63.