Value through Innovation19 December 2014
29 August 2012

Large scale registry shows atrial fibrillation management is suboptimal and unequal around the world

Worldwide, one in ten patients presenting in the emergency department with atrial fibrillation will die within one year

Munich, Germany, August 29, 2012 – New one-year follow-up results from the global RE-LY AF registry, a multinational primary care registry, have been announced for the first time during the European Society of Cardiology (ESC) Congress 2012. The findings show that 11.7% of patients with atrial fibrillation (AF) who were included in the registry from January 2008 to April 2011 had died within one year.1 The registry mainly reflects data from patients before novel oral anticoagulants became available.

Data from over 15,000 patients in 47 countries across the world, including low income countries have been reviewed.2 The new insights underline the high unmet medical need and the large opportunities for improvement by applying already available strategies and tools for diagnosis, risk assessment, and treatment of patients with AF.

The one-year results presented today show wide variations in the management and outcomes of AF patients and affirm that stroke prevention in AF remains a major issue worldwide:1

  • The one-year mortality rate appears to be highly variable between countries. While it was significantly lower in Western Europe than in North America (8.3% vs 11.4%), it was about twice as high in Africa and Latin America (20.0% and 18.1% respectively)
  • Despite the availability of anticoagulant therapy, like vitamin K antagonists, more than 4% of AF patients experienced a stroke within one year
  • Significantly more patients with AF suffered a stroke in the regional cohorts examined in China (7.2%), South East Asia (6.6%) and Africa (8.3%) compared to North America (3.1%). Most of the differences in stroke rate seen between regions can be explained by differing treatment usage of vitamin K antagonists such as warfarin

"Registries such as RE-LY AF have demonstrated clear differences in the management and outcomes of patients with atrial fibrillation in different regions of the world and suggest that there is an opportunity to use existing knowledge to improve the care of patients with atrial fibrillation worldwide. For example, the introduction of new oral anticoagulant medications may have a particularly important benefit in China and South-East Asia, where warfarin is infrequently used and when it is used, lower INR values are usually targetted," commented Dr Jeff Healey, McMaster University, Hamilton, Canada. "These findings have important implications for the improvement of disease management and health policy, aimed at protecting AF patients from the severe outcomes of this disease."

The first baseline results from the RE-LY AF registry showed that the presentation, etiology and treatment of AF vary greatly between geographic regions.2 With regard to stroke prevention through anticoagulation, baseline results showed:

  • Worldwide, appropriate use of traditional oral anticoagulants was low, with wide variations between regions
  • INR (International Normalized Ratio) control was poor, with only North America and Europe exceeding levels above 50% time in therapeutic range (INR 2.0-3.0).

"The insights resulting from this large registry once again confirm the worldwide medical need for alternatives to vitamin K antagonists which are difficult to manage for stroke prevention in patients with non-valvular AF," commented Prof. Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. "Based on the RE-LY® trial results and the great body of clinical experience, we are confident Pradaxa® can and will play an important role in helping to close this treatment gap."

NOTES TO THE EDITORS

RE-LY AF Registry1,2
RE-LY AF is the first prospective registry to report one-year outcomes for a large cohort of primary care patients with AF from all regions of the world, including low-income countries. It is based on the clinical records of patients presenting to emergency departments with AF between January 2008 and April 2011 from academic settings, rural and urban areas in 9 major geographic regions of the world. The goals of the RE-LY AF registry, supported by Boehringer Ingelheim, are to measure worldwide variations in the predisposing conditions and treatment of AF, with a focus on blood pressure management and anticoagulation.

Stroke prevention in atrial fibrillation
AF is the most common sustained heart rhythm condition,3 with one in four adults over the age of 404 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.4,5 Up to three million people worldwide suffer strokes related to AF each year.6-9 Strokes due to AF tend to be severe, with an increased likelihood of death (20%), and disability (60%).10

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.11-15 Appropriate anticoagulation therapy can help to prevent many types of AF-related strokes and improve overall patient outcomes.16

The risk of stroke is measured using a risk assessment scale called CHADS2. This is a scoring system (0 to 6) used to indicate a patient's risk for a thromboembolic stroke and used for anticoagulation strategies. One point is given for any of the following conditions: C, congestive heart failure; H, hypertension; A, age 75 years old or greater; D, diabetes mellitus; and S, stroke which receives 2 points. The European Society of Cardiology (ESC) guidelines17 issued in 2010 recommend that if a patient has a CHADS2 score of 2 and above, oral anticoagulation therapy (OAC) such as warfarin (target INR of 2-3) or one of the new OAC drugs (such as dabigatran) should be prescribed.

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.18,19 Given AF-related strokes tend to be more severe, this results in higher direct medical patient costs annually.20 The total societal burden of AF-related stroke reaches €13.5 billion per year in the European Union alone.20

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%21) open label warfarin.22,23 Patients were followed-up in the study for a median of 2 years with a minimum of 1 year follow-up.22

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: 22,23

  • 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)24 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.

References
1Healey JS, et al.Global Variations in the 1-Year Rates of Death and Stroke in 15,340 Patients Presenting to the Emergency Department with Atrial Fibrillation in 47 Countries: The RE-LY AF Registry. Presented at the European Society of Cardiology Congress 2012, 29th August 2012.
2Healey JS, et al. Global variation in the etiology and management of atrial fibrillation: results from a global atrial fibrillation registry- Presented at the European Society of Cardiology Congress 2011, August 2011, session number 711006.
3Stewart S, Murphy NF, Walker A, McGuire A, McMurray JJ. Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK. Heart 2004;90:286-92.
4Lloyd-Jones DM, Wang TJ, Leip EP, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation 2004;110:1042-6.
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7Atlas of Heart Disease and Stroke, World Health Organization, September 2004. Viewed Dec 2010 at http://www.who.int/cardiovascular_diseases/en/cvd_atlas_15_burden_stroke.pdf
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18Coyne KS, Paramore C, Grandy S, et al. Assessing the direct costs of treating nonvalvular atrial fibrillation in the United States. Value Health 2006;9:348-56.
19Ringborg A, Nieuwlaat R, Lindgren P et al. Costs of atrial fibrillation in five European countries: results from the Euro Heart Survey on atrial fibrillation. Europace 2008;10:403-11.
20Brüggenjürgen B, Rossnagel K, Roll S, et al. The impact of atrial fibrillation on the cost of stroke: the Berlin acute stroke study. Value Health 2007;10:137-43
21Pradaxa European Summary of Product Characteristics, 2012
22Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009; 361:1139-51.
23Connolly SJ, et al. Newly identified events in the RE-LY trial. N Engl J Med. 2010;363:1875-6.
24Di Nisio M, et al. Direct thrombin inhibitors. N Engl J Med 2005; 353:1028-40.

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