Trial results of Pradaxa® vs ASA in ESUS published in NEJM
- First Phase III randomised clinical trial to compare dabigatran etexilate and acetylsalicylic acid (ASA)
- No significant difference in recurrent stroke prevention after ESUS
- Dabigatran showed no significant difference in major bleeding
Ingelheim, Germany, 16 May 2019 - Boehringer Ingelheim today announced full results from the RE-SPECT ESUS® trial, a Phase III randomised, double-blind study investigating the efficacy and safety of Pradaxa® (dabigatran etexilate) versus acetylsalicylic acid (ASA) in preventing recurrent stroke in patients with embolic stroke of undetermined source (ESUS). The results were published in the New England Journal of Medicine (NEJM).1
The trial did not meet its primary endpoint, which was to show a clinically significant difference between dabigatran etexilate and ASA on reducing the risk of a recurrent stroke among post-stroke patients with ESUS. However, a post-hoc analysis showed a treatment effect emerged in favour of dabigatran after one year.1 The safety results from the trial demonstrated that the risk of major bleeding was not significantly different between dabigatran etexilate and ASA. 1 A comparable low risk for the most serious bleeding outcomes, such as intracranial haemorrhage, was shown. 1
As the first ever comparative trial to investigate dabigatran etexilate versus ASA, the results add to the wealth of evidence supporting the established safety profile of dabigatran etexilate, which has already been demonstrated in its approved indications in the extensive RE-VOLUTION® clinical trial and registry programme.2-24
“The results from RE-SPECT ESUS provide highly interesting information, showing that dabigatran had a similar low risk of major bleeding compared to ASA in this high-risk population of post-stroke patients. This clearly reaffirms the positive risk-benefit profile of dabigatran,” said Dr Waheed Jamal, Corporate Vice President, Head of CardioMetabolic Medicine, Boehringer Ingelheim.
ESUS is a type of cryptogenic stroke, which is when an ischaemic stroke has an unknown cause.25 A stroke is classified as an ESUS when other potential diagnoses have been ruled out.25,26 Overall, one in six ischaemic strokes are classified as ESUS.25 Following an ESUS, most patients are treated with anti-platelet therapy, such as ASA27 ; however, one in three go on to have a recurrent stroke within five years.28
Pradaxa is not approved in any country for patients with ESUS.
RE-SPECT-ESUS - Professor Hans-Christoph Diener – Senior Professor for Clinical Neurosciences, Department of Neurology, University Hospital Essen, Germany
RE-SPECT-ESUS – David Z. Rose, MD – Professor of Vascular Neurology, University of South Florida and Tampa, United States
About the RE-SPECT ESUS trial
Randomised, double-blind, evaluation in secondary stroke prevention comparing the efficacy and safety of the oral thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid (ASA) in patients with embolic stroke of undetermined source (RE-SPECT ESUS®)1
RE-SPECT ESUS® was a Phase III, double-blind trial of dabigatran vs ASA for secondary stroke prevention in patients with ESUS and involved 5,390 patients from more than 40 countries. Patients were randomised to receive dabigatran etexilate 150 mg BID, adjusted to 110mg BID for patients above 75 years or with impaired renal function, and a placebo matching ASA 100 mg or ASA 100 mg and a placebo matching dabigatran etexilate. The primary endpoint of the trial was to show a clinically significant difference between dabigatran etexilate and ASA on the risk of a recurrent stroke among post-stroke patients with ESUS.1
Boehringer Ingelheim
Improving the health of humans and animals is the goal of the research-driven pharmaceutical company Boehringer Ingelheim. The focus in doing so is on diseases for which no satisfactory treatment option exists to date. The company therefore concentrates on developing innovative therapies that can extend patients’ lives. In animal health, Boehringer Ingelheim stands for advanced prevention.
Family-owned since it was established in 1885, Boehringer Ingelheim is one of the pharmaceutical industry’s top 20 companies. Some 50,000 employees create value through innovation daily for the three business areas human pharmaceuticals, animal health and biopharmaceuticals. In 2018, Boehringer Ingelheim achieved net sales of around 17.5 billion euros. R&D expenditure of almost
3.2 billion euros, corresponded to 18.1 per cent of net sales.
As a family-owned company, Boehringer Ingelheim plans in generations and focuses on long-term success. The company therefore aims at organic growth from its own resources with simultaneous openness to partnerships and strategic alliances in research. In everything it does, Boehringer Ingelheim naturally adopts responsibility towards mankind and the environment.
More information about Boehringer Ingelheim can be found on www.boehringer-ingelheim.com or in our annual report: http://annualreport.boehringer-ingelheim.com.
Intended audiences:
This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. It is directed to the international audience outside Germany. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business.
References
1 Diener HC et al. Dabigatran for Prevention of Stroke after Embolic Stroke of Undetermined Source. N Engl J Med 2019; 380:1906-1917.
2 Connolly SJ et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-51.
3 Connolly SJ et al. Newly identified events in the RE-LY trial. N Engl J Med. 2010;363:1875-76.
4 Connolly SJ et al. Additional Events in the RE-LY Trial. N Engl J Med. 2014;371:1464–5.
5 Connolly SJ et al. The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study. Circulation. 2013;128:237–43.
6 Ezekowitz MD et al. Long-term evaluation of dabigatran 150 vs. 110 mg twice a day in patients with non-valvular atrial fibrillation. Europace. 2016;18:973–8.
7 Cannon CP et al. Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. N Engl J Med. 2017;377:1513–24.
8 Calkins H et al. Uninterrupted Dabigatran versus Warfarin for Ablation in Atrial Fibrillation. N Engl J Med. 2017;376:1627–36.
9 Pollack CV et al. Idarucizumab for Dabigatran Reversal - Full Cohort Analysis. N Engl J Med. 2017;377:431–41.
10 Pollack CV et al. Idarucizumab for Dabigatran Reversal. N Engl J Med. 2015;373:511–20.
11 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 Thomb Haemost. 2007;5:2178–85.
12 RE-MOBILIZE Writing Committee et al. Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplasty. 2009;24:1–9.
13 Eriksson BI et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet 2007;370:949–56.
14 Eriksson BI et al. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, double-blind, non-inferiority trial. Thromb Haemost. 2011;105:721–9.
15 Schulman S et al. Dabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism. N Engl J Med. 2009;361:2342–52.
16 Schulman S et al. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014;129:764–72.
17 Schulman S et al. Extended Use of Dabigatran, Warfarin, or Placebo in Venous Thromboembolism. N Engl J Med. 2013;368:709–18.
18 Eikelboom JW et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369:1206–14.
19 Diener HC et al. Design of Randomized, double-blind, Evaluation in secondary Stroke Prevention comparing the EfficaCy and safety of the oral Thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid in patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS). Int J Stroke. 2015;10:1309–12.
20 Ferro. JM. et al. Randomized evaluation of the safety and efficacy of dabigatran etexilate versus dose adjusted warfarin in patients with cerebral venous thrombosis (RE-SPECT CVT). Presented on Tuesday 10 May at the 2nd European Stroke Organisation Conference 2016, Barcelona, Spain.
21 Ageno W et al. RE-COVERY DVT/PE: Rationale and design of a prospective observational study of acute venous thromboembolism with a focus on dabigatran etexilate. Thromb Haemost. 2017;117:415–21.
22 Huisman MV et al. The Changing Landscape for Stroke Prevention in AF: Findings From the GLORIA-AF Registry Phase 2. J Am Coll Cardiol. 2017;69:777–85.
23 Huisman MV et al. Design and rationale of Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation: a global registry program on long-term oral antithrombotic treatment in patients with atrial fibrillation. Am Heart J.2014;167:329–34.
24 Fanikos J et al. RE-VECTO: Idarucizumab drug administration surveillance program results. The Congress on Open Issues in Thrombosis and Hemostasis 2018 jointly with the 9th Russian Conference on Clinical Hemostasiology and Hemorheology. Abstract;68
25 Hart RG et al. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol. 2014;13:429–38.
26 Saver JL. Cryptogenic Stroke. N Engl J Med. 2016;374:2065–74.
27 Hart RG et al. Embolic Stroke of Undetermined Source: A Systematic Review and Clinical Update. Stroke. 2017:48;867–72.
28 Ntaios G et al. Embolic Strokes of Undetermined Source in the Athens Stroke Registry: An Outcome Analysis. Stroke. 2015;46:2087–93.