New European survey highlights ischaemic stroke protection as treatment priority for patients with atrial fibrillation

New findings from a pan-European online survey of 1,000 physicians have demonstrated that for over two thirds of physicians, preventing ischaemic stroke is the most important treatment goal for patients with atrial fibrillation (AF).1 Ischaemic stroke is the most common type of stroke suffered by patients with AF2, and as such physicians across Europe have highlighted the vital need for increased awareness of the true incidence and impact in this patient population. The survey findings were announced in parallel with the European Stroke Conference in London (28th-31st May) and highlight the need for additional information and education about the risk and impact of ischaemic stroke on the lives of AF patients.

Every year, up to three million patients with AF have a stroke.3,4 92% of strokes in AF patients are ischaemic.2 They occur when a blood vessel supplying the brain with blood is blocked e.g. by a blood clot. This reduction or complete prevention of blood flow to the brain may result in severe and burdensome physical impairment, paralysis or even death.5 Atrial fibrillation is the most common sustained heart rhythm condition6 affecting approximately 2% of the total population.7 The condition leads to a five-fold increase in the risk of stroke.7

“Every physician who treats patients with atrial fibrillation needs to recognise the risk of ischaemic stroke in these patients,” commented Professor Hans-Christoph Diener, Professor of Neurology and Chairman of the Department of Neurology, University of Essen, Germany. “Today, we have great and new possibilities at hand to prevent many of these devastating events. It is our responsibility as treating physicians to identify the patients in need for stroke prevention through screening, diagnosis and risk assessment and then protect them as best as we can from the possible consequences of an ischaemic stroke or an intracranial haemorrhage.”

Cardiologists and general practitioners (GPs) in seven European countries were surveyed via a MedLIVETM PULSE online survey to ascertain their perspectives on treatment priorities in AF. The survey explored factors affecting prescribing behaviours, such as the importance of stroke prevention in AF, the comparative need for treatment experience and convenience, and the perceived awareness of the incidence of ischaemic stroke. Key findings demonstrated:1

• 67% of physicians state that preventing ischaemic stroke is the most important treatment goal for patients with AF
• 84% of physicians highlight the vital need for awareness of the impact of ischaemic strokes for patients with AF, stating that the true incidence may be underestimated*
• When questioned on important factors that affect prescribing decisions, 56% of physicians responded that protecting patients against ischaemic stroke is the single most important factor affecting their prescribing decisions, followed by general treatment efficacy (protection against all strokes) and treatment safety (minimising the risk of bleeding in patients)
• When asked which attributes were most important when choosing treatments for patients with AF, 50% of physicians stated that the availability of clinical data was the most important attribute to consider and 39% selected experience in clinical practice over the treatment’s convenience for daily management

“Ischaemic stroke is a real concern; not only because the risk is so high, but also because of the potential life-changing impact that it may have on patients with atrial fibrillation. Ischaemic strokes can be devastating for both patients and their families, and have a significant impact on their daily lives. They also increase healthcare utilisation and the need for long-term care,” stated Trudie Lobban, MBE, Founder & CEO of Atrial Fibrillation Association (AFA). “It is essential that more work is undertaken to raise awareness of the risk of ischaemic stroke and to ensure that patients with AF receive treatments that provide the most comprehensive protection.”

Appropriate anticoagulation therapy can help to prevent strokes experienced by patients with AF and improve overall outcomes.8 Major treatment guidelines in Europe, the US and worldwide recognise the benefits of anticoagulant treatments for stroke prevention in atrial fibrillation.9 Pradaxa® (dabigatran etexilate) 150mg bid is the only novel oral anticoagulant, for which its trial (RE-LY®**, comparing Pradaxa® vs. warfarin) has shown a relevant reduction of ischaemic stroke: In patients with non-valvular AF, Pradaxa® 150mg reduced the risk for ischaemic stroke by 25% compared to warfarin.10,11 In addition, patients taking Pradaxa® 150mg had a 59% lower risk of intracranial bleeding, the most feared side-effect of anticoagulation.10,11

Overall in the RE-LY® trial, Pradaxa® 150mg bid provided a 35% reduction in the overall risk of stroke and systemic embolism versus warfarin.10,11Pradaxa® 110mg bid was shown to be non-inferior compared to warfarin for the prevention of stroke and systemic embolism.10,11 Pradaxa® 150mg showed a similar risk of major bleeds versus warfarin and Pradaxa® 110mg bid demonstrated significantly lower major bleeding.10,11 Both doses of Pradaxa® were associated with significantly lower total, intracranial and life-threatening bleeding compared to warfarin.10,11

Clinical experience of Pradaxa® exceeds that of all other novel oral anticoagulants: It equates to over 1.6 million patient-years in all licensed indications and spans over 100 countries worldwide.12

About the Survey1

The survey was conducted via a MedLIVETM PULSE to 1,000 GPs and Cardiologists in France, Germany, Spain, Italy, Belgium, The Netherlands and Ireland on behalf of Boehringer Ingelheim GmbH. The survey consisted of five key questions in English language, with responses received from 556 GPs and 444 Cardiologists. The survey explored factors affecting prescribing behaviours in atrial fibrillation, including the respective importance of treatment attributes and the perceived overall incidence of ischaemic stroke, and provided consensus on the need for ischaemic stroke prevention to become a treatment priority.

Stroke Prevention in Atrial Fibrillation

AF is the most common sustained heart rhythm condition6, with one in four adults over the age of 406 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.7 Up to three million people worldwide suffer strokes related to AF each year.3,4 Strokes due to AF tend to be severe, with an increased likelihood of death (20%), and disability (60%).5

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.2 Appropriate anticoagulation therapy can help to prevent many types of AF-related strokes and improve overall patient outcomes.8 Pradaxa® 150mg bid is the only novel oral anticoagulant, for which the pivotal trial vs. warfarin has shown a statistically significant and clinically relevant reduction of both ischaemic and haemorrhagic strokes.10,11 Additionally, treatment with Pradaxa® is associated with >2-fold lower rates of both fatal and non-fatal intracranial haemorrhage, one of the most devastating complications of anticoagulation therapy.13,14

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.15,16 Given AF-related strokes tend to be more severe, this results in higher direct medical patient costs annually.17 The total societal burden of AF-related stroke reaches €13.5 billion per year in the European Union alone.9

The RE-LY® trial

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 open label warfarin (INR 2.0-3.0, median TTR 67%18).10,11 Patients were followed-up in the study for a median of 2 years with a minimum of 1 year follow-up.10

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).10

Compared to well controlled warfarin, dabigatran etexilate showed in the trial:10,11

• Significant reduction in the risk of stroke and systemic embolism – including ischaemic 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, similar rates with dabigatran etexilate 150 mg bid
• Significantly lower life threatening and intracranial bleeding with both doses
• Significant reduction in vascular mortality with dabigatran etexilate 150mg bid.

Dabigatran etexilate

Dabigatran etexilate was the first 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.

Clinical experience of Pradaxa® in all licensed indications already corresponds to over 1.6 million patient-years in over 100 countries worldwide.12 One patient year equates to the treatment of a single patient over a whole year (365 days). The expression of clinical experience in patient years provides a more realistic assessment of experience with a treatment than the mere number of patients treated without relation to their individual treatment time.

References

1. MedLIVE PULSE online survey, data on file with Boehringer Ingelheim.
2. Andersen KK, et al. Hemorrhagic and ischemic strokes compared: stroke severity, mortality, and risk factors. Stroke. 2009;40:2068−72.
3. Atlas of Heart Disease and Stroke, World Health Organization, September 2004. Viewed Nov 2012 at http://www.who.int/cardiovascular_diseases/en/cvd_atlas_15_burden_stroke.pdf
4. Camm JA, et al. Guidelines for the management of atrial fibrillation. Eur Heart J. 2010;31:2369–429.
5. Gladstone DJ, et al. Potentially Preventable Strokes in High-Risk Patients With Atrial Fibrillation Who Are Not Adequately Anticoagulated. Stroke. 2009;40:235-240.
6. Lloyd-Jones DM, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004;110:1042-6.
7. Camm JA, et al. 2012 focussed update of the ESC Guidelines for the management of atrial fibrillation. Eur Heart J. 2012;33:2719-41.
8. Aguilar MI, Hart R. Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. Cochrane Database of Systematic Reviews. 2005, Issue 3. Art. No.: CD001927.
9. Fuster V, et al. ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation – executive summary. Circulation. 2006;114:700-52.
10. Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-51.
11. Connolly SJ, et al. Newly identified events in the RE-LY® trial. N Engl J Med. 2010;363(19):1875-76.
12. Boehringer Ingelheim data on file.
13. Hart RG, et al. Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with Warfarin or Dabigatran: The RE-LY® Trial. Stroke. 2012; 43(6):1511-1517.
14. Fang MC, et al. Death and disability from warfarin-associated intracranial and extracranial hemorrhages. Am J Med. 2007; 120:700 –705.
15. Coyne KS, et al. Assessing the direct costs of treating nonvalvular atrial fibrillation in the United States. Value Health 2006; 9:348-56.
16. 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.
17. 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.
18. Pradaxa® European Summary of Product Characteristics.
19. Di Nisio M, et al. Direct thrombin inhibitors. N Engl J Med 2005;353:1028-40.

*The survey did not ask the polled physicians for potential reasons why the true incidence of ischaemic stroke may be underestimated. Potential influencing factors may include the challenge of detecting silent events and/or cryptogenic strokes without routine implementation of screening tests.

**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 (110 mg bid and 150 mg bid) each administered in a blinded manner, with open label warfarin.10,11