Anniversary of the pivotal RE-LY® trial marks a decade of innovation for stroke prevention in AF patients

Ingelheim, Germany, 30 August 2019 - Boehringer Ingelheim today announces the ten-year anniversary of the RE-LY^® trial publication^1-3 recognising the contribution made in the decade since by patients, healthcare professionals (HCPs) and researchers.

In the fifty years prior, warfarin had been the standard of care for stroke prevention in atrial fibrillation (SPAF). While effective, warfarin has a number of known interactions, meaning patients require careful monitoring, and the warfarin dose being adjusted accordingly. The pivotal RE-LY^® trial investigated the efficacy and safety in stroke prevention of dabigatran compared to warfarin in 18,113 atrial fibrillation (AF) patients. It marked the first time that a non-vitamin K antagonist oral anticoagulant (NOAC), that has since been brought to market, was shown to be at least as effective and safer than warfarin in stroke prevention in a randomised setting.^1-3 This represented the first puzzle piece in the growing knowledge base around NOACs as an alternative therapy option to vitamin K antagonists (VKAs) for SPAF.

“RE-LY^® was the first crucial sign that a new, safer therapy option for SPAF was on its way,” said Stuart  J. Connolly, MD, Professor Emeritus, Division of Cardiology at McMaster University in Hamilton, Ontario. “The positive results brought a real sense of excitement to researchers, HCPs and patients alike, and the subsequent approval of dabigatran for SPAF from 2010 onwards provided a safer, effective and more manageable therapy option. AF patients now had greater reassurance around stroke prevention and without the impact that regular monitoring and dose adjustment had on their day-to-day life.”

RE-LY^® was just the start of the journey. The design, evaluation and subsequent approval of the first and only widely-available specific reversal agent (idarucizumab) in 2015 added to the bigger picture of understanding and reassured patients that the effects of dabigatran could be quickly and effectively reversed for emergency surgery / urgent procedures and in life-threatening or uncontrolled bleeding.^5,6

“Today, Boehringer Ingelheim continues to deliver on its commitment to patients with high unmet need in the cardiovascular space and beyond,” said Dr Waheed Jamal, Corporate Vice President, Head of CardioMetabolic Medicine, Boehringer Ingelheim. “Thank you to the patients, HCPs and researchers who have helped and continue to help develop and expand access to safer and innovative therapies that improve the care of patients with a range of cardiometabolic conditions.”

About Stroke Prevention in Atrial Fibrillation (SPAF)
AF  is the most common sustained heart rhythm condition.  It can lead to a five-fold increase in the risk of ischaemic stroke for the 33.5 million people living with AF around the world. ,  15 million people worldwide suffer a stroke each year. One–third of these people die as a consequence. 

About RE-LY^®
The RE-LY^® trial, which was published in the New England Journal of Medicine in September 2009, compared dabigatran to warfarin for preventing stroke in patients with AF.^1-3 In the RE-LY^® trial, 18,113 patients with non-valvular atrial fibrillation and a risk of stroke were investigated, using a PROBE (prospective, randomised, open label with blinded endpoint evaluation) design to assess the safety and efficacy of dabigatran 150mg or 110mg twice daily vs. dose-adjusted warfarin.¹¹

Trial results demonstrated that dabigatran had notable advantages over warfarin even when warfarin is well controlled.^1-3 Compared to warfarin:

• Dabigatran 150mg twice daily was superior for the prevention of stroke / SE and significantly reduced the risk of both ischaemic and haemorrhagic stroke^1-3,11
  • Rates of the primary outcome were 1.12% per year in the group that received 150mg of dabigatran (relative risk, 0.65; 95% CI, 0.52 to 0.81; P<0.001)
  • Rates of the primary outcome were 1.72% per year in the warfarin group, as compared with 1.54% per year in the group that received 110 mg of dabigatran (relative risk with dabigatran, 0.89; 95% confidence interval [CI], 0.73 to 1.09; P=0.89)^1-3,12
• Dabigatran significantly reduced the risk of intracranial haemorrhage (ICH), along with significant reductions in the risk of both life threatening and total bleeding ^1-3,12​^​
  • The rate of major bleeding was 3.61% per year in the warfarin group, as compared with 2.92% per year in the group receiving 110 mg of dabigatran (P=0.003) ^1-3,12
  • The rate of major bleeding was 3.40% per year in the group receiving 150 mg of dabigatran (P=0.41)​ 

About Pradaxa^® (dabigatran etexilate)
Clinical experience of Pradaxa^® equates to over 10 million patient-years in all licensed indications worldwide. Pradaxa® has been in the market for more than eight years and is approved in over 100 countries.⁴
 
Currently approved indications for Pradaxa^® are:^5,6

• 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 deep vein thrombosis (DVT) and pulmonary embolism (PE) and the prevention of recurrent DVT and recurrent PE in adults

Dabigatran, 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.^13-15 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, dabigatran 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.^4,12

Pradaxa^® is the only non-vitamin K antagonist oral anticoagulant with an approved, widely available reversal agent. Praxbind^® is approved in the European Union and United States for adult patients treated with Pradaxa^® who require rapid reversal of its anticoagulant effects prior to urgent procedures/emergency surgery or in life threatening or uncontrolled bleeding.^5,6

About Boehringer Ingelheim
Improving the health of humans and animals is the goal of the research-driven pharmaceutical company Boehringer Ingelheim. The focus in doing so is on diseases for which no satisfactory treatment option exists to date. The company therefore concentrates on developing innovative therapies that can extend patients’ lives. In animal health, Boehringer Ingelheim stands for advanced prevention.

Family-owned since it was established in 1885, Boehringer Ingelheim is one of the pharmaceutical industry’s top 20 companies. Some 50,000 employees create value through innovation daily for the three business areas human pharmaceuticals, animal health and biopharmaceuticals. In 2018, Boehringer Ingelheim achieved net sales of around 17.5 billion euros. R&D expenditure of almost 3.2 billion euros, corresponded to 18.1 per cent of net sales.

As a family-owned company, Boehringer Ingelheim plans in generations and focuses on long-term success. The company therefore aims at organic growth from its own resources with simultaneous openness to partnerships and strategic alliances in research. In everything it does, Boehringer Ingelheim naturally adopts responsibility towards mankind and the environment.

More information about Boehringer Ingelheim can be found on www.boehringer-ingelheim.com or in our annual report: http://annualreport.boehringer-ingelheim.com.

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Intended audiences:
This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. It is directed to the international audience outside Germany. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business.

References

1   Connolly. SJ. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2010;361:1139-51.
2   Connolly. SJ. et al. Newly identified events in the RE-LY trial. N Engl J Med. 2009;363:1875-76.
3   Connolly. SJ. et al. Correspondence: Additional Events in the RE-LY Trial. N Engl J Med. 2014.
4   Data on file. Available upon request.
5   Praxbind^® US prescribing information.
6   Praxbind^® European Summary of Product Characteristics.
7   Lloyd Jones. DM. et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004;110(9):1042-46.
8   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.
9   Chugh SS et al. Worldwide Epidemiology of Atrial Fibrillation: A Global Burden of Disease 2010 Study. Circulation. 2014;129:837–847.
10 World Stroke Organization. Facts and figures about stroke. Available from: https://www.world-stroke.org/component/content/article/16-forpatients/84-facts-and-figures-about-stroke. Last accessed: June 2019.
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;157:805-10.
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):1511-17.
13 Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–95.
14 Di Nisio M. et al. Direct thrombin inhibitors. N Engl J Med.2005;353:1028–40.
15 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.