New long-term treatment data confirms consistent benefit and safety profile of Pradaxa® beyond 6 years

• Pradaxa® (dabigatran etexilate) is the only novel oral anticoagulant with more than 6 years of long-term data supporting its beneficial role for stroke prevention in atrial fibrillation1
• The efficacy and safety profiles of both doses of Pradaxa® during up to 6.7 years of extended treatment remain consistent with the pivotal results seen in the registration trial RE-LY®1,2,3
• Presented during the American Heart Association's Scientific Sessions, new data add to the body of evidence for Pradaxa®

For media outside of the US, the UK & Canada only

Ingelheim, Germany, 19 November 2013 – Results from a new combined analysis of the pivotal Phase III RE-LY® trial and its extension study RELY-ABLE® show that, in long-term treatment, the efficacy and safety profiles of both doses of Pradaxa® (dabigatran etexilate, 150mg bid and 110mg bid) remain consistent with the results seen in the 18,000 patient-strong RE-LY® registration trial.1,2,3 The new data were presented during the American Heart Association’s Scientific Sessions 2013.

"This is important news for physicians and patients who use either dose of dabigatran etexilate to reduce the lifetime risk of stroke associated with atrial fibrillation," said Prof. Michael D. Ezekowitz, Thomas Jefferson Medical College, Philadelphia, USA. "They can feel reassured that dabigatran etexilate will provide sustained stroke prevention and a favourable long-term safety profile."

The combined analysis includes all patients from RE-LY® and RELY-ABLE® who were treated with either Pradaxa® 150mg bid or Pradaxa® 110mg bid. Median follow-up lasted an average of 4.6 years, with maximum follow-up extending to 6.7 years in several hundred patients. The new findings show that for Pradaxa®:1

  • The rates of stroke or systemic embolism were 1.25 and 1.54 percent / year on dabigatran 150mg bid and 110mg bid respectively
    • The rates of ischaemic stroke were 1.03 and 1.29 percent / year on dabigatran 150mg bid and 110mg bid respectively
    • The rates of major haemorrhage were 3.34 and 2.76 percent / year on dabigatran 150mg bid and 110mg bid respectively
  • The rates of major haemorrhage were 3.34 and 2.76 percent / year on dabigatran 150mg bid and 110mg bid respectively
  • The safety profile was consistent over time, with no new safety issues identified compared to the original RE-LY® results
    Prof. Dr. Klaus Dugi
    Prof. Dr.
    Klaus Dugi


"These unique long-term treatment results presented during the AHA Scientific Sessions show consistent safety and efficacy profiles for both doses of Pradaxa® over more than 6 years of clinical follow-up," said Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. "Among the novel oral anticoagulants, such long-term data are only available for Pradaxa®. Especially for a chronic condition that requires life-long treatment like stroke prevention in atrial fibrillation, results such as these provide key insights for physicians and patients."

The favourable efficacy-safety profile of Pradaxa® is supported by safety assessments from regulatory authorities including the European Medicines Agency and the U.S. Food and Drug Administration (FDA).4,5 Clinical experience with Pradaxa® continues to grow and equates to over two million patient-years in all licensed indications to date.6 Pradaxa® is the longest studied novel oral anticoagulant.6

Pradaxa® is currently approved in over 100 countries worldwide for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and for the primary prevention of venous thromboembolism following total hip replacement or total knee replacement surgery.6,7

NOTES TO THE EDITORS

About Pradaxa® (dabigatran etexilate)
Clinical experience of Pradaxa® (dabigatran etexilate) exceeds that of all other novel oral anticoagulants, equating to over 2 million patient-years in all licensed indications worldwide.6 Pradaxa® has already been in the market for more than 5 years and is approved in over 100 countries.6 Currently approved indications for Pradaxa® are:7

  • Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) and a risk factor for stroke
  • Primary prevention of venous thromboembolic events in patients undergoing elective total hip replacement surgery
  • Primary prevention of venous thromboembolic events in patients undergoing elective total knee replacement surgery

In June 2013 Boehringer Ingelheim started submitting new applications to regulatory authorities for Pradaxa® for the following indications:6

  • Treatment of acute deep vein thrombosis (DVT) and/or pulmonary embolism (PE) and prevention of related death
  • Prevention of recurrent deep vein thrombosis (DVT) and/or pulmonary embolism (PE) and related death

Important Notice: Pradaxa® is currently not approved for the acute treatment or prevention of recurrent DVT and/or PE7

Pradaxa®, a direct reversible 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.7,8 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.9 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 dose adjustment.8,10

About Pradaxa® and Stroke Prevention in Atrial Fibrillation (AF)​
Pradaxa® 150mg bid is the only novel oral anticoagulant, for which its pivotal trial vs. warfarin has shown a statistically significant reduction in both haemorrhagic and ischaemic strokes when compared to warfarin.2,3 Pradaxa® 110mg bid was as effective as warfarin in overall stroke risk reduction.2,3 These results were shown in RE-LY®, a phase III PROBE (prospective, randomized, open-label with blinded endpoint evaluation) trial.2,3,11 Additionally, treatment with Pradaxa® was associated with great reductions in intracranial haemorrhage, one of the most devastating complications of anticoagulation therapy.12​

Stroke Prevention in Atrial Fibrillation (AF)
AF is the most common sustained heart rhythm condition, with one in four adults over the age of 40 developing the condition in their lifetime.13 People with AF are more likely to experience blood clots, which increases the risk of stroke by five-fold.14 Ischaemic strokes are the most common type of AF-related stroke, accounting for 92% of strokes and frequently leading to severe debilitation.15,16​

Appropriate anticoagulation therapy has been proven to be highly effective in preventing AF-related strokes and saving patients from its consequences.17

For further information on the prevalence, medical background and societal burden of AF please visit: http://www.newshome.com/af-stroke.aspx​

About the Pradaxa® (dabigatran etexilate) clinical trial programme
Since its discovery, Pradaxa® has been evaluated through the extensive RE-VOLUTION® clinical trial programme, which includes 10 clinical trials involving more than 40,000 patients in over 100 countries globally, encompassing studies in:1-3,11,18-26

 

  • Stroke prevention in AF
  • Primary prevention of VTE in patients undergoing elective total hip replacement surgery
  • Primary prevention of VTE in patients undergoing elective total knee replacement surgery
  • Treatment of acute DVT or PE
  • Prevention of recurrent DVT or PE

In line with Boehringer Ingelheim’s commitment to research and scientific development the clinical trial programme for Pradaxa® is ongoing.

About RE-LY®
The pivotal RE-LY® trial was designed to investigate the efficacy and safety of Pradaxa® in stroke prevention in patients with non-valvular atrial fibrillation. RE-LY® (Randomized Evaluation of Long term anticoagulant therapY) was a global, phase III, PROBE (prospective, randomized, open-label with blinded endpoint evaluation) trial of 18,113 patients enrolled in over 900 centres in 44 countries designed to compare two fixed doses of the oral direct thrombin inhibitor Pradaxa® (dabigatran etexilate 110mg and 150mg bid) each administered in a blinded manner, with open label warfarin (INR 2.0-3.0, median TTR 67%7).2,3,11​

For further information on study design, objectives and endpoints please visit http://www.newshome.com/af-stroke/atrial-fibrillation-stroke/rely-relyable-backgrounder.aspx​

About RELY-ABLE®
RELY-ABLE® (Long Term Multi-Center Extension of Dabigatran Treatment in Patients with Atrial Fibrillation) was designed to provide additional information on the long-term effects of the two doses of Pradaxa® (dabigatran etexilate) in patients who had completed RE-LY®. The 5,851 enrolled patients continued to receive the same double-blind dose of Pradaxa® as they did in the RE-LY® study. Patients randomised to warfarin in RE-LY® were not eligible for RELY-ABLE®. From the beginning of RE-LY® to the end of RELY-ABLE®, the median duration of follow-up for patients was over 4 years, with the longest duration reported at 6.7 years. The outcomes were consistent with the results observed during the RE-LY® trial.1,26​

For further information on study design, objectives and endpoints please visit http://www.newshome.com/af-stroke/atrial-fibrillation-stroke/rely-relyable-backgrounder.aspx​

About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 140 affiliates and more than 46,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

Social responsibility is a central element of Boehringer Ingelheim's culture. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavours.

In 2012, Boehringer Ingelheim achieved net sales of about 14.7 billion euro. R&D expenditure in the business area Prescription Medicines corresponds to 22.5% of its net sales. For more information please visit www.boehringer-ingelheim.com

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., the UK or Canada.

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Referências

  1. Ezekowitz M, et al. RE-LY and RELY-ABLE: Long-term Follow-up of Patients With Non-valvular Atrial Fibrillation Receiving Dabigatran Etexilate for Up to 6.7 Years. Oral presentation #10684 on Monday 18 November 2013 at the American Heart Association’s Scientific Sessions, Dallas, Texas, USA.
  2. Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-51.
  3. Connolly SJ, et al. Newly identified events in the RE-LY trial. N Engl J Med. 2010;363:1875-6.
  4. FDA Drug Safety Communication: Update on the risk for serious bleeding events with the anticoagulant Pradaxa (dabigatran) – 2 November 2012 http://www.fda.gov/Drugs/drugsafety/ucm326580.htm Last accessed 11 November 2013.
  5. European Medicines Agency Press release - 25 May 2012: EMA/337406/2012. European Medicines Agency updates patient and prescriber information for Pradaxa. http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2012/05/news_detail_001518.jsp&mid=WC0b01ac058004d5c1 Last accessed 11 November 2013.
  6. Boehringer Ingelheim data on file.
  7. Pradaxa® European Summary of Product Characteristics 2013.
  8. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–95.
  9. Di Nisio M, et al. Direct thrombin inhibitors. N Engl J Med. 2005;353:1028–40.
  10. Stangier J, et al. Pharmacokinetic Profile of the Oral Direct Thrombin Inhibitor Dabagitran Etexilate in Healthy Volunteers and Patients Undergoing Total Hip Replacement. J Clin Pharmacol. 2005;45:555–63.
  11. Ezekowitz MD, et al. Rationale and design of RE-LY®: Randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran. Am Heart J. 2009;157(5):805-10.
  12. Hart RG, et al. Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with Warfarin or Dabigatran: The RE-LY® Trial. Stroke. 2012;43(6):1511-7.
  13. Lloyd-Jones DM, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004;110(9):1042-46.
  14. 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.
  15. Andersen KK, et al. Hemorrhagic and ischemic strokes compared: stroke severity, mortality, and risk factors. Stroke. 2009;40(6):2068-72.
  16. Gladstone DJ, et al. Potentially Preventable Strokes in High-Risk Patients With Atrial Fibrillation Who Are Not Adequately Anticoagulated. Stroke. 2009;40:235-240.
  17. Aguilar MI, Hart R. Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. Cochrane Database of Syst Rev. 2005;(3):CD001927.
  18. Eriksson BI. et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet. 2007;370:949–56.
  19. Eriksson BI. et al. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, doubleblind, non-inferiority trial. Thromb Haemost. 2011;105(4):721-9.
  20. Eriksson BI. et al. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost. 2007;5:2178–85.
  21. Ginsberg JS. et al. Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthoplasty. 2009;24(1)1–9.
  22. Schulman S. et al. Dabigatran versus warfarin in the Treatment of Acute Venous Thromboembolism. N Engl J Med. 2009;361:2342–52.
  23. Schulman S. et al. A Randomized Trial of Dabigatran Versus Warfarin in the Treatment of Acute Venous Thromboembolism (RE-COVER II). Oral presentation from Session 332: Antithrombotic Therapy 1. Presented on 12 December at the American Society of Hematology (ASH) Annual Meeting 2011.
  24. Schulman S. et al. Extended Use of Dabigatran, Warfarin or Placebo in Venous Thromboembolism. N Engl J Med. 2013;368:709–18.
  25. Oldgren J. et al. Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial. Eur Heart J. 2011;32:2781-9.
  26. Connolly S.J. et al. The Long Term Multi-Center Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) study. Circulation. 2013;128(3):237-43.