PRADAXA® (dabigatran etexilate) first drug in 50 years to gain approval for stroke prevention in atrial fibrillation in Europe
Posted: 4 August 2011 | | No comments yet
Pradaxa®1 (dabigatran etexilate) approved…
The European Commission (EC) today approved Boehringer Ingelheim’s breakthrough oral anticoagulant, Pradaxa®1 (dabigatran etexilate2) for the prevention of stroke in patients with atrial fibrillation (AF) at risk of stroke. This EU label extension means that, for the first time in over 50 years, millions of AF patients across Europe will have access to a new treatment for the prevention of AF-related strokes which is effective and convenient3,4, and has demonstrated a good safety profile.
The EC has approved the use of dabigatran etexilate in the EU for the prevention of stroke and systemic embolism in adult patients with non-valvular AF with one or more risk factors. Previous stroke, transient ischemic attack, or systemic embolism (SEE); Left ventricular ejection fraction < 40 %; Symptomatic heart failure, ≥New York Heart Association (NYHA) Class 2; Age ≥75 years; Age ≥65 years associated with one of the following: diabetes mellitus, coronary artery disease, or hypertension.
While overall the 150mg bid dose is recommended for the majority of patients, the 110mg bid dose is specifically available for elderly patients aged 80 years or above, for patients at increased risk of bleeding and for patients who are co-administered with dabigatran etexilate and the calcium channel blocker verapamil.
In 2008 dabigatran etexilate was granted EU approval for the primary prevention of venous thromboembolic events (blood clots) in adults who have undergone elective total hip or elective total knee replacement surgery. Speaking of the new EU label extension for the prevention of stroke in patients with AF, Professor Gregory Lip, Consultant Cardiologist & Professor of Cardiovascular Medicine, University of Birmingham Centre for Cardiovascular Sciences, Birmingham, United Kingdom commented, “The approval of dabigatran etexilate in Europe represents a major advance in the treatment of this condition. For the past 50 years physicians worldwide have been waiting for an alternative to vitamin K antagonist therapies, such as long time standard of care, warfarin.” He continued, “Whilst effective, warfarin has many limitations such as the need for regular monitoring and various food-drug and drug-drug interactions, resulting in only half of eligible patients receiving warfarin and fewer than half of these patients being controlled within the desired therapeutic range.”
Trudie Lobban, CEO of the Atrial Fibrillation Association added, “Atrial fibrillation raises the risk of stroke by five times, resulting in up to three million people worldwide suffering strokes related to this condition each year. Atrial fibrillation-related strokes are particularly severe and disabling, with one half of this population dying within one year after a stroke.”
The approval of dabigatran etexilate for stroke prevention in AF patients is based on the groundbreaking results from RE-LY®, one of the largest studies ever conducted in AF including over 18,000 patients. RE-LY® was a PROBE (prospective, randomized, open-label with blinded endpoint evaluation) trial, comparing two fixed doses of the oral direct thrombin inhibitor dabigatran etexilate (110mg and 150mg bid) each administered in a blinded manner, with open label warfarin.3-5
Dabigatran etexilate 150mg bid is the only novel oral anticoagulant approved for stroke prevention in AF in Europe that has been proven superior to well-controlled warfarin (median TTR 67%)5. Dabigatran etexilate 150mg bid reduced the risk of stroke and systemic embolism by 35% while also significantly lowering the risk of life-threatening and intracranial bleeding, compared to well-controlled warfarin.3,4Dabigatran etexilate 110mg bid has been shown non-inferior to warfarin in reducing the risk of stroke and systemic embolism with a significantly lower rate of major bleeding.
Dr. Stuart Connolly, co-principal investigator of RE-LY®, Director, Division of Cardiology at McMaster University and member of The Population Health Research Institute, Hamilton, Ontario added, “The landmark RE-LY®study results also showed us that dabigatran etexilate is consistently effective at preventing strokes across a wide range of patients with AF, irrespective of age, gender, stroke risk, type of atrial fibrillation, prior stroke, and comorbidities such as hypertension and diabetes.”
In addition to the approval in Europe, dabigatran etexilate has already been approved for the prevention of stroke in atrial fibrillation in the US, Canada, Japan, Australia and several other countries across four continents.1,6-9 In 2008 dabigatran etexilate was granted EU approval for the primary prevention of venous thromboembolic events (blood clots) in adults who have undergone elective total hip or elective total knee replacement surgery.
“The approval of dabigatran etexilate in Europe marks an important milestone in the history of Boehringer Ingelheim and also in the continuing fight for improved prevention of stroke, a disease which continues to have a large unmet need,” said Professor Andreas Barner,Chairman of the Board of Managing Directors, Boehringer Ingelheim. “It is a result of nearly 20 years of innovative research and development by our scientists. We will now ensure that this new breakthrough treatment is made available to physicians and atrial fibrillation patients throughout Europe as soon as possible.”
- Pradaxa®, Summary of Product Characteristics, 2011. Europe.
- Di Nisio M, et al. Direct Thrombin Inhibitors. N Engl J Med 2005; 353:1028-40.
- Connolly SJ, et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009; 361:1139-51.
- Connolly SJ, Ezekowitz MD, Yusuf S, Reilly PA, Wallentin L: Newly identified events in the RE-LY® trial. N Engl J Med 2010; 363(19): 1875-1876.
- FDA Advisory Committee Briefing Document, September 2010,http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisory Committee/UCM226009.pdf.
- U.S. Food and Drug Administration – Pradaxa® Prescribing Information.Oct 19th, 2010.
- Health Canada – PRADAX™ Product Monograph. Oct 26th, 2010.
- Prazaxa® product information, January 2011, Japan.
- Pradaxa®, Australian Product information, approved April 29th, 2011.
- Stewart S, Murphy N, Walker A, et al. Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK. Heart 2004; 90:286-92.
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- Atlas 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.
- Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991: 22(8);983-8.
- Marini C, De Santis F, Sacco S, et al. Contribution of atrial fibrillation to incidence and outcome of ischaemic stroke: results from a population-based study. Stroke 2005; 36:1115-9.
- Lin HJ, Wolf PA, Kelly-Hayes M, et al. Stroke severity in atrial fibrillation: the Framingham study. Stroke 1996; 27:1760-4.
- Hart RG, Pearce LA, Aguilar MI, et al. Meta-Analysis: antithrombotic therapy to prevent stroke in patients who have non-valvular atrial fibrillation. Ann Intern Med 2007;146:857-67.
- Bruggenjurgen B et al. The Impact of Atrial Fibrillation on the Cost of Stroke: The Berlin Acute Stroke Study. Value Health 2007; 10: 137–43.