Value through Innovation04 February 2016
06 June 2012

FDA affirms superiority of Pradaxa® (dabigatran etexilate) 150mg over warfarin in reduction of both ischaemic and haemorrhagic strokes

Ingelheim, Germany, June 6, 2012 – Boehringer Ingelheim has today announced that it has updated the US prescribing information for Pradaxa® (dabigatran etexilate) in alignment with the US Food and Drug Administration (FDA) to affirm that "Pradaxa® 150mg twice daily was superior in reducing ischemic and hemorrhagic strokes relative to warfarin."1 This positive change to the US label is based upon the results of the pivotal RE-LY® trial conducted in 18,000 patients with non-valvular atrial fibrillation, which demonstrated unequivocally the superior benefits offered by Pradaxa® in terms of effective prevention of stroke. In addition, RE-LY demonstrated a significant benefit vs. well controlled warfarin in life-threatening bleeding events, and major reductions in intracranial bleeding.2,3,‡

"Ischaemic strokes account for up to 92% of strokes suffered by patients with atrial fibrillation, often leading to severe debilitation and poor prognosis," said Hans-Christoph Diener, M.D., Ph.D., Professor and Chairman, Department of Neurology, University Duisburg-Essen, Germany. "For patients with atrial fibrillation, reducing the risk of stroke, especially ischaemic stroke, is the primary goal of anticoagulation treatment. It is important for both physicians and patients to have a treatment option that offers this decisive clinical benefit over warfarin when considering long term prevention from stroke."

Pradaxa® 150mg bid is the only novel oral anticoagulant which has shown in a major study a significant reduction of both ischaemic and haemorrhagic strokes in patients with non-valvular atrial fibrillation when compared to warfarin.2,3 The RE-LY® trial showed that Pradaxa® 150mg bid reduced the risk of stroke and systemic embolism by 35% compared to well-controlled warfarin (INR 2-3, median TTR 67%4).2,3 Furthermore, Pradaxa® 110mg bid, which is indicated for certain patients, was shown to be as effective as well-controlled warfarin in the prevention of stroke and systemic embolism, while being associated with significantly lower major bleeding events in patients with non-valvular AF. RE-LY® was a PROBE trial (prospective, randomized, open-label with blinded endpoint evaluation), comparing two fixed doses of the oral direct thrombin inhibitor dabigatran etexilate (110mg and 150mg bid) each administered in a blinded manner, with open label warfarin.2,3

Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim

Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim

"We welcome this update to the US prescribing information for Pradaxa® which clearly demonstrates the unique benefit offered by this novel treatment to patients and physicians worldwide," said Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. "By significantly reducing both ischaemic and haemorrhagic strokes, and at the same time providing significant reductions in intracranial bleeding, Pradaxa® 150mg twice daily has the potential to protect patients from catastrophic events better than warfarin."

The effectiveness and favourable safety profile of Pradaxa® has been well documented in an extensive clinical trial programme2-7, passing independent regulatory scrutiny and approval worldwide. Clinical experience of Pradaxa® is already well established and continues to grow, equating to over 780,000 patient years in over 70 countries8 and exceeding that of all other novel oral anticoagulants.9 The launch of Pradaxa® has been the most successful in the history of Boehringer Ingelheim and is among the pharmaceutical industry's top launches in the last decade.

Boehringer Ingelheim remains focused on both patients' benefit and safety and is further investigating the profile of Pradaxa® in the long-term safety study RELY-ABLE, the results of which will be presented later this year. Additionally, Boehringer Ingelheim recently launched Phase II of the GLORIA-AF patient registry, which is designed to gain insights into the use of antithrombotic treatments in clinical practice to reduce the risk of stroke in patients with non-valvular atrial fibrillation.


About AF and stroke
AF is the most common sustained heart rhythm condition,10 with one in four adults over the age of 4011 developing the condition in their lifetime. People with AF are more likely to experience blood clots, which increases the risk of stroke by five-fold.11,12 Up to three million people worldwide suffer strokes related to AF each year.13-16 Strokes due to AF tend to be severe, with an increased likelihood of death (20%), and disability (60%).17 Many AF-related strokes can be prevented with appropriate antithrombotic therapy.18 AF-related strokes currently represent a significant cost to healthcare systems across Europe. Given AF-related strokes tend to be more severe this results in direct medical patient costs which are higher than non AF-related strokes annually (€11,799 vs €8,817 P < 0.001).19

About RE-LY®
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 dabigatran (110mg and 150mg bid) each administered in a blinded manner, with well controlled (INR 2.0-3.0, median TTR 67%4) open label warfarin.2,3 Patients were followed-up in the study for a median of 2 years with a minimum of 1 year follow-up.2
The primary endpoint of the trial was incidence of stroke (including haemorrhagic) or systemic embolism. Secondary outcome measures included all-cause death, incidence of stroke (including haemorrhagic), systemic embolism, pulmonary embolism, acute myocardial infarction, and vascular death (including death from bleeding).
Compared to well controlled warfarin, dabigatran etexilate showed in the trial: 2,3

  • Significant reduction in the risk of stroke and systemic embolism – including haemorrhagic strokes with dabigatran etexilate 150mg bid
  • Similar rates of stroke/systemic embolism with dabigatran etexilate 110mg bid
  • Significantly lower major bleeding events with dabigatran etexilate 110mg bid
  • Significantly lower life threatening and intracranial bleeding with both doses
  • Significant reduction in vascular mortality with dabigatran etexilate 150mg bid.

About dabigatran etexilate
Dabigatran etexilate is at the forefront of a new generation of oral anticoagulants/direct thrombin inhibitors (DTIs)20 targeting a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases.

Potent antithrombotic effects are achieved with direct thrombin inhibitors by specifically blocking the activity of thrombin (both free and clot-bound), the central enzyme in the process responsible for clot (thrombus) formation. In contrast to vitamin-K antagonists, which variably act via different coagulation factors, dabigatran etexilate provides effective, predictable and consistent anticoagulation with a low potential for drug-drug interactions and no drug-food interactions, without the need for routine coagulation monitoring or dose adjustment.

About the dabigatran etexilate clinical trial programme
Boehringer Ingelheim’s clinical trial programme 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 surgery
  • Treatment of acute VTE
  • Secondary prevention of VTE
  • Stroke prevention in AF
  • Prevention of thromboembolism after heart valve replacement.

Boehringer Ingelheim

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 44,000 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.

As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. 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 endeavors.

In 2011, Boehringer Ingelheim achieved net sales of about 13.2 billion euro. R&D expenditure in the business area Prescription Medicines corresponds to 23.5% of its net sales.

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 USA, UK or Canada.

Pradaxa US Prescribing Information. 2012.
2Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361:1139-51.
3Connolly SJ, et al. Newly identified events in the RE-LY® trial. N Engl J Med 2010; 363(19):1875-6.
4Pradaxa®, European Summary of Product Characteristics, 2012.
5Schulman S, et al. Dabigatran etexilate versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009; 361:2342-52.&nbsp;
6Eriksson 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.
7Eriksson 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.
8Data on file.
9Eikelboom JW, et al. Does dabigatran improve stroke-prevention in atrial fibrillation? Reply to a rebuttal. J Thromb Haemost 2010; 8:1438–9.
10Stewart S, et al. Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK. Heart 2004; 90:286-92.
11Lloyd-Jones DM, et al.&nbsp; Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation 2004; 110:1042-6.&nbsp;
12Fuster V, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation – executive summary. Circulation 2006; 114:700-52.
13Global Atlas on Cardiovascular Disease Prevention and Control, World Health Organization in collaboration with the World Heart Federation and the World Stroke Organization 2011. Viewed May 2012 at 14Atlas of Heart Disease and Stroke, World Health Organization, September 2004. Viewed Dec 2010 at cvd_atlas_15_burden_stroke.pdf .
15Wolf PA, et al. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991: 22(8);983-8.
16Marini C, et al. Contribution of atrial fibrillation to incidence and outcome of ischaemic stroke: results from a population-based study. Stroke 2005; 36:1115-9.
17Lin HJ, et al. Stroke severity in atrial fibrillation: the Framingham study. Stroke 1996; 27:1760-4.
18Hart RG, et al. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have non-valvular atrial fibrillation. Ann Intern Med 2007; 146:857-67.
19Bruggenjurgen B, et al. The Impact of Atrial Fibrillation on the Cost of Stroke: The Berlin Acute Stroke Study. Value Health 2007; 10: 137–43.
20Di Nisio M, et al. Direct Thrombin Inhibitors. N Eng J Med 2005; 353:1028-40.

‡ RE-LY® was a PROBE trial (prospective, randomized, open-label with blinded endpoint evaluation), comparing two fixed doses of the oral direct thrombin inhibitor dabigatran etexilate (110mg and 150mg bid) each administered in a blinded manner, with open label warfarin.

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