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

Posted: 5 November 2012 | | No comments yet

“We welcome the positive conclusions reached…”

Boehringer Ingelheim logo

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

“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.

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.

* 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.
  6. Fuster V, et al. ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation – executive summary. Circulation. 2006;114:700-52.
  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
  9. Wolf PA, et al. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22:983-8.
  10. Marini 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
  11. Gladstone DJ, et al. Potentially Preventable Strokes in High-Risk Patients With Atrial Fibrillation Who Are Not Adequately Anticoagulated. Stroke. 2009;40:235-240.
  12. Paolucci S, et al. Functional outcome of ischemic and hemorrhagic stroke patients after inpatient rehabilitation. Stroke. 2003;34:2861−5.
  13. Petrea RE, et al. Gender differences in stroke incidence and poststroke disability in the Framingham Heart Study. Stroke. 2009;40:1032-7.
  14. Meschia JF, et al. Genetic susceptibility to ischemic stroke. Nat Rev Neurol. 2011;7:369−78.
  15. Andersen KK, et al. Hemorrhagic and ischemic strokes compared: stroke severity, mortality, and risk factors. Stroke.2009;40:2068−72.
  16. Roger VL, et al. AHA Statistical Update. Heart Disease and Stroke Statistics—2011 Update. A Report From the American Heart Association. Circulation. 2011;123:e18−e209.
  17. Hart 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.
  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.
  27. Di Nisio M, et al. Direct thrombin inhibitors. N Engl J Med 2005; 353:1028-40.

Related organisations

Related people

Related diseases & conditions

Send this to a friend