Ingelheim, Germany, 15 March 2010 - Data presented today at the 59 th Annual Scientific Session of the American College of Cardiology have shown greater reductions in stroke in patients with atrial fibrillation (AF) for dabigatran etexilate * compared to the current standard of care, warfarin, irrespective of a patient’s risk profile for stroke.1 The new sub-group analysis from the landmark RE-LY® study ** assessed the rate of stroke and systemic embolism in patients defined as being at low (n=5,775), moderate (n=6,455) and high (n=5,882) risk of such events by the validated stroke risk stratification score, CHADS 2. 1,2

The RE-LY® sub-group analysis showed that dabigatran etexilate 150mg bid reduced the rate of stroke and systemic embolism compared with well-controlled warfarin, irrespective of a patient’s stroke risk. Dabigatran etexilate 110mg bid resulted in similar reductions as well-controlled warfarin. Both doses were associated with lower major bleeding rates in patients at low risk of stroke. 1

In detail, the results showed: 1

  • Dabigatran etexilate 150mg bid reduced the rate of stroke and systemic embolism when compared with well-controlled warfarin across all stroke risk groups with the relative risk (RR) being 0.62 (0.38−1.02) in low, 0.61 (0.40−0.92) in moderate, and 0.70 (0.52−0.95) in high risk patients
  • Dabigatran etexilate 110mg bid showed similar reductions in the rate of stroke and systemic embolism to well-controlled warfarin, with RR being 1.00 (0.65−1.55) in low, 1.04 (0.73−1.49) in moderate and 0.79 (0.59−1.06) in high risk patients
  • Both doses of dabigatran etexilate were associated with lower rates of major bleeding compared to well-controlled warfarin in low risk patients (D110mg RR: 0.67 (0.49−0.90), D150mg RR: 0.73 (0.54−0.98)).
  • Consistent with the overall RE-LY results both doses of dabigatran were associated with substantial reductions in the rates of intracranial hemorrhage in all risk groups

Lead author Dr Jonas Oldgren, Uppsala University Hospital, Sweden said, “For healthcare professionals treating patients with atrial fibrilliation at risk of stroke and systemic embolism, this sub-group analysis is very encouraging as it shows that dabigatran etexilate 150mg bid is the first treatment reducing strokes more than warfarin across the full spectrum of stroke risk in patients with AF.”

Stroke risk stratification scores such as CHADS 2 have been developed to guide appropriate use of anticoagulant therapy in patients with AF to maximise its benefit. 2 For patients defined as being at high or moderate risk of stroke, the reduction in stroke risk with vitamin K antagonists (VKAs), such as warfarin, is likely to outweigh the risk of bleeding. 3 For patients with a low risk CHADS 2 score, the benefits of VKAs are not as clear. Therefore, currently many patients only receive Aspirin, which is less effective than warfarin in reducing the risk of stroke, leaving patients insufficiently protected from the threat of severe and highly debilitating strokes. 4-7

Dr Jonas Oldgren continues, “Healthcare professionals and patients have long been waiting for a treatment that can provide stroke prevention across all levels of risk. We have shown that Dabigatran etexilate provides greater benefits in stroke reduction across patients at low, medium and high risk, as well as reduced bleeding vs. warfarin in patients at low risk. This provides important evidence of the clear benefit that this novel oral anticoagulant can provide over current treatment with VKAs, such as warfarin.”

Up to three million people worldwide suffer strokes related to AF each year, 8-10 which tend to be especially severe and disabling, 8 with half of people dying within one year. 11

Notes to Editors

About RELY®

RE-LY® (Randomized Evaluation of Long term anticoagulant therapy) was a global, phase III, randomized trial of 18,113 patients enrolled in over 900 centres in 44 countries, investigating whether dabigatran etexilate (2 blinded doses) is as effective as well controlled warfarin with target INR of 2.0-3.0 for stroke prevention. Patients were followed-up in the study for a median of 2 years with a minimum of 1 year follow-up.

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:12

  • Significant reduction in the risk of stroke and systemic embolism – including haemorrhagic strokes
  • Significantly lower bleeding – including life threatening and intracranial bleeding
  • Significant reduction in vascular mortality.

About AF and stroke

AF is the most common heart rhythm condition, affecting around 1% of the total population, rising to 10% in people over the age of 80. 13 A total of 6.3 million people in the US, Japan, Germany, Italy, France, UK and Spain were living with AF in 2007 and this is expected to increase to 7.5 million by 2017 primarily due to the ageing population. 14 People with AF are at increased risk of blood clots, which raises stroke risk by five times. 3,15 Up to 3 million people worldwide suffer strokes related to AF each year. 8-10 Strokes due to AF tend to be severe, with an increased likelihood of death (20%), and disability (60%), with resultant societal costs and burden to the healthcare system. 8 AF alone is associated with a cost of up to €13.5 billion across the European Union. 3 Warfarin is the current standard of care for reducing stroke in patients with AF. It is highly effective when patients blood clotting value is maintained within the narrow therapeutic INR range of 2.0-3.0 as in a clinical trial setting. 16 However in clinical practice, due to the well-known limitations with warfarin only 51% of diagnosed patients with AF at risk of stroke receive warfarin 17 and fewer than half of these are controlled within the narrow therapeutic range. 18

About Dabigatran etexilate

Dabigatran etexilate is at the forefront of a new generation of oral anticoagulants/direct thrombin inhibitors (DTIs) 19 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.

Dabigatran etexilate has already been approved and is widely utilized in over 50 countries under the trademark Pradaxa® for the primary prevention of venous thromboembolic events (blood clots) in adults who have undergone elective total hip or elective total knee replacement surgery.

About the dabigatran etexilate clinical trial program

Boehringer Ingelheim’s clinical trial program 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 surgeries
  • Treatment of acute VTE
  • Secondary prevention of VTE
  • Secondary prevention of cardiac events in patients with acute coronary syndrome (ACS)
  • Stroke prevention in atrial fibrillation (AF)

Please be advised

This release is from the Corporate Headquarters of Boehringer Ingelheim and is intended for international markets. This being the case, please be aware that there may be some differences between countries regarding specific medical information including licensed uses. Please take account of this when referring to the material.

About Boehringer Ingelheim

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 138 affiliates in 47 countries and 41,300 employees. Since it was founded in 1885, the independent, family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2008, Boehringer Ingelheim posted net sales of 11.6 billion euro while spending one fifth of net sales in its largest business segment Prescription Medicines on research and development.

* Dabigatran etexilate is being investigated for the prevention of stroke in patients with atrial fibrillation.

** Randomized Evaluation of Long-Term Anticoagulant Therapy