Value through Innovation04 February 2016
05 November 2012

FDA and EMA reaffirm important health benefits and safety of Pradaxa® (dabigatran etexilate) for patients with atrial fibrillation

  • New FDA data safety assessment supports previous clinical evidence on the safety of the anticoagulation therapy and reports new Pradaxa® and warfarin patients to have similar bleeding rates
  • Comprehensive efficacy and safety evaluation by the EMA leads to recommendation for renewal of the marketing authorisation for Pradaxa® to ensure ongoing patient benefit

Ingelheim, Germany, 05 November, 2012 – Following independent regulatory appraisals of the safety and efficacy of the anticoagulation therapy Pradaxa®, both the U.S. Food and Drug Administration (FDA) and European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) have reconfirmed the positive benefit-risk profile of the treatment for prevention of stroke in patients with atrial fibrillation (AF)*.

On Friday 2nd November, the FDA published the results of a Mini-Sentinel assessment that indicated the bleeding rates associated with new use of Pradaxa ® are not higher than those associated with new use of warfarin.1 With this analysis the FDA further confirmed the results demonstrated by the landmark 18,000-patient RE-LY® trial, upon which the treatment was approved. The announcement of the results follows the FDA’s U.S. label update in June this year. The U.S. Label affirms superior reduction in ischemic and hemorrhagic stroke versus warfarin in patients with non-valvular atrial fibrillation.

* The reconfirmation of the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) includes both indications of Pradaxa®: for prevention of stroke in patients with atrial fibrillation and for prevention of venous thromboembolism.

The FDA Mini-Sentinel assessment evaluated new information about the risk of serious bleeding associated with use of the anticoagulants Pradaxa® and warfarin. The FDA investigated the rates of gastrointestinal bleeding and intracranial haemorrhage for new users of Pradaxa® compared to new users of warfarin. The assessment was undertaken using insurance claims and administrative data from the FDA’s Mini-Sentinel pilot of the Sentinel Initiative.

Specifically, the FDA states: "For the populations in the Mini-Sentinel data assessment, the combined incidence rate (ICH and GIH events* per 100,000 days at risk) was 1.8 to 2.6 times higher for new users of warfarin than for new users of Pradaxa."1
Further, "The FDA has not changed its recommendations regarding Pradaxa. Pradaxa provides an important health benefit when used as directed."1

This follows the positive opinion adopted by the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) on the renewal of the marketing authorisation for Pradaxa® in October.2

The CHMP’s recommendation for renewal of the marketing authorisation for the next five years supports the benefits that Pradaxa® has been delivering to patients since its first approval in March 2008. The recommendation was based upon the favourable risk-benefit profile of the treatment, confirmed by the CHMP following comprehensive evaluation and includes all licensed indications of the treatment.1

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

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

"We welcome the positive conclusions reached by both the EMA’s CHMP Committee and the FDA in relation to the risk-benefit profile of Pradaxa®," commented Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. "The renewal of the marketing authorisation in Europe will reassure both, healthcare professionals and patients, of the benefit from this highly effective anticoagulant. Furthermore, the FDA’s assessment is a clear cut statement for Pradaxa’s favourable safety profile, now demonstrated also in real-world clinical practice."

Boehringer Ingelheim will present a wealth of latest data on Pradaxa® from 16 abstracts at the American Heart Association’s (AHA) Scientific Sessions in Los Angeles from 3-7 November 2012, including the first and only long-term safety and efficacy data of an oral anticoagulant, the results of the RELY-ABLE™ study. The data reinforce Boehringer Ingelheim’s ongoing commitment to adding to the scientific body of evidence for Pradaxa® and the benefit of the treatment for stroke prevention in atrial fibrillation.

To view the full FDA announcement, click here:

To view the EMA CHMP announcement, click here:

Stroke prevention in atrial fibrillation
AF is the most common sustained heart rhythm condition,4 with one in four adults over the age of 405 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.5,6 Up to three million people worldwide suffer strokes related to AF each year.7-10 Strokes due to AF tend to be severe, with an increased likelihood of death (20%), and disability (60%).11

Ischaemic strokes are the most common type of AF-related stroke, accounting for 92% of strokes experienced by AF patients and frequently leading to severe debilitation.12-16 Appropriate anticoagulation therapy can help to prevent many types of AF-related strokes and improve overall patient outcomes.17

Worldwide, AF is an extremely costly public health problem, with treatment costs equating to $6.65 billion in the US and over €6.2 billion across Europe each year.19,20 Given AF-related strokes tend to be more severe, this results in higher direct medical patient costs annually.21 The total societal burden of AF-related stroke reaches €13.5 billion per year in the European Union alone.6

About VTE
Venous thromboembolism (VTE) refers to a condition in which a blood clot (thrombus) forms in a vein. Most commonly, it develops in the deep veins of the leg or pelvis and is known as deep vein thrombosis (DVT). An embolism occurs if the clot, or its part, breaks off from the site where it forms and travels through the venous system. If the clot lodges in the lung a potentially fatal condition, pulmonary embolism (PE), occurs.

VTE is the third most common cardiovascular disorder after coronary heart disease and stroke,22 affecting approximately 1.5 million Europeans23 and 3 million Americans24 each year. In Europe, it kills more than twice as many people as AIDS, breast cancer, prostate cancer, and traffic accidents combined.23 In addition, up to half of people with DVT may develop the chronic post thrombotic syndrome (PTS) and 4% may develop chronic thromboembolic pulmonary hypertension.25,26

Given its prevalence, associated morbidity, mortality and chronic complications, VTE is a costly condition which puts a significant burden on both the healthcare systems and individuals. Annual costs of VTE are estimated to be more than $1.5 billion in the US and €3.0 billon in Europe.25,26

About dabigatran etexilate
Dabigatran etexilate is at the forefront of a new generation of oral anticoagulants/direct thrombin inhibitors (DTIs)27 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.

* ICH and GIH= Intracranial hemorrhage (brain bleeding) and gastrointestinal hemorrhage (bleeds in pharynx, stomach, colon or rectum)


1. Food and Drug Administration FDA Drug Safety Communication: Update on the risk for serious bleeding events with the anticoagulant Pradaxa. Viewed November 2012
2. European Medicines Agency: Opinions on annual re-assessments, renewals of marketing authorisations and accelerated assessment procedures. Adopted at the CHMP meeting of 15-18 October 2012. Viewed October 2012
3. Pradaxa® European Summary of Product Characteristics, 2012.
4. Stewart S, et al. Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK. Heart. 2004;90:286-92.
5. Lloyd-Jones DM, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004;110:1042-6.
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7. Global 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
8. Atlas of Heart Disease and Stroke, World Health Organization, September 2004. Viewed Dec 2010 at
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18. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Europace. 2010 Oct: 12:1360-420.
19. Coyne KS, et al. Assessing the direct costs of treating nonvalvular atrial fibrillation in the United States. Value Health. 2006;9:348-56.
20. Ringborg A, et al. Costs of atrial fibrillation in five European countries: results from the Euro Heart Survey on atrial fibrillation. Europace. 2008;10:403-11.
21. Brüggenjürgen B, et al. The impact of atrial fibrillation on the cost of stroke: the Berlin acute stroke study. Value Health. 2007;10:137-43
22. 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 (11), 2178–85.
23. Cohen AT, et al. Venous thromboembolism (VTE) in Europe. Thromb Haemost.2007;98:756–64
24. White RH.The epidemiology of venous thromboembolism. Circulation 2003;107[23 suppl 1]:I4-I8.
25. Hansson PO, et al. Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors. Arch Intern Med 2000;160:769–74
26. Pengo V, Lensing A, Prins M, et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Eng J Med 2004;350:2257-64.
Di Nisio M, et al. Direct thrombin inhibitors. N Engl J Med 2005; 353:1028-40.

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