ESC Congress 2014 Hot Line Session: Favourable effect of Pradaxa on kidney function over time compared to warfarin

• RE-LY® sub-analysis shows that Pradaxa® treatment favourably affects kidney function1 deterioration over time compared to warfarin
• Data provide additional support for long-term use of Pradaxa® in stroke prevention in non-valvular atrial fibrillation (NVAF)1

Non-US/Non-UK/Non-Canadian Media

Ingelheim, Germany, 2 September 2014 – New data presented today indicate that kidney function decline is less pronounced in patients with an irregular heartbeat (non-valvular atrial fibrillation, NVAF) who are treated with Pradaxa® (dabigatran etexilate) compared to warfarin.1 A natural decline in kidney function is expected as part of the ageing process or as a result of other underlying diseases.2 New data support that long-term Pradaxa® treatment compares favourably to warfarin in terms of kidney function decline over time.1 The new RE-LY® study sub-analysis findings were presented today at a Clinical Trial Update Hot Line session during the ESC Congress 2014 organised by the European Society of Cardiology in Barcelona.1

Professor Michael Böhm
Professor
Michael Böhm

"These data support dabigatran as a good long-term treatment option for non-valvular atrial fibrillation patients," said Professor Michael Böhm, Director of the Department of Internal Medicine and Cardiology at the University Hospital of Saarland, Homburg/Saar, Germany. "These RE-LY® study findings may have particular relevance for NVAF patients who have co-existing medical conditions which negatively impact their kidney function, such as diabetes, and for patients with poorly controlled vitamin K antagonist therapy. Dabigatran may provide additional benefit to these patients in the long term."

The data included in the ESC Congress 2014 Hot Line session were derived from a post hoc exploratory analysis of the RE-LY® study that included over 18,000 patients and compared kidney function change in patients treated with either warfarin or Pradaxa® (110mg or 150mg twice daily).1​

Results indicate that kidney function deteriorated more in patients on warfarin compared to those on either dose of Pradaxa®.1 Results were significantly different to warfarin for both doses of Pradaxa® at 30 months, with similar patterns seen in different Pradaxa® subgroups.1 Patients who were poorly controlled on warfarin and spent more time above the recommended International Normalized Ratio target range (INR 2-3) experienced a markedly sharper decline in kidney function compared to patients taking Pradaxa®.1 Patients with diabetes, who are at generally higher risk of kidney problems were particularly susceptible to the effects of warfarin, and experienced higher rates of kidney decline than non-diabetic NVAF patients.1 The same was true for patients previously treated with warfarin.1 Also in these patients, Pradaxa® treatment compared favourably to warfarin.1

While the exact mechanism behind this difference has yet to be identified, there is a well-defined pathophysiological background. Vitamin K is known to protect against the build-up of calcium deposits in blood vessels, known as vascular calcification.3 Oral anticoagulation with vitamin K-antagonists such as warfarin, which block vitamin K in the body, have been associated with an increased rate of vascular calcification and vascular damage.3 Pradaxa® is an oral direct thrombin inhibitor which does not interfere with vitamin K, but works in a different way to reduce blood clotting in order to protect patients with non-valvular atrial fibrillation against stroke.4,5,6​

NOTES TO THE EDITORS

About Pradaxa® (dabigatran etexilate)​
The landmark RE-LY® study results for Pradaxa® were first presented five years ago in Barcelona at the ESC Congress 2009. Since then, the RE-LY® study findings have been reconfirmed in countless sub-analyses, supported by Regulatory Authorities worldwide and were most recently replicated outside of a clinical study setting by an independent FDA assessment involving 134,000 Medicare patients with AF.7-9

In the United States, the licensed doses for dabigatran etexilate are 150mg twice daily and 75mg twice daily for the prevention of stroke and systemic embolism in adult patients with non-valvular AF.10 The dose of 75 mg twice daily is not authorised in Europe for this indication.5

The positive efficacy and safety profile of Pradaxa® has been well recognised in clinical trials11-19 as well as in the real world.7-9 The treatment has been available for more than 6 years and is approved in over 100 countries worldwide where it is now providing substantial stroke protection benefits to NVAF patients. Clinical experience of Pradaxa® exceeds that of all other novel oral anticoagulants, equating to 2.4 million patient-years in all licensed indications worldwide.20

Currently approved indications for Pradaxa® are:5,10

  • Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and a risk factor for stroke
  • Primary prevention of venous thromboembolic events in patients undergoing elective total hip replacement surgery or total knee replacement surgery
  • Treatment of DVT and PE and the prevention of recurrent DVT* and recurrent PE* in adults

Pradaxa®, a direct thrombin inhibitor (DTI), was the first widely approved drug in a new generation of direct oral anticoagulants, available to target a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases.4,5 Potent antithrombotic effects are achieved with direct thrombin inhibitors by specifically blocking the activity of thrombin, the central enzyme in the process responsible for clot (thrombus) formation.6 In contrast to vitamin-K antagonists, which variably act via different coagulation factors, Pradaxa® provides effective, predictable and reproducible anticoagulation with a low potential for drug-drug interactions and no drug-food interactions, without the need for routine coagulation monitoring or mandatory dose adjustment.4,21

Treatment with Pradaxa® in patients with severe kidney impairment (creatinine clearance < 30 ml/min) is contraindicated.5,10 Healthcare professionals are required to assess the kidney function of patients in different situations (e.g. before treatment initiation or when a decline in kidney function is suspected [e.g. hypovolemia, dehydration and with certain concomitant medications]).5,10 In patients aged above 75 or with kidney impairment, kidney function should be assessed at least yearly whilst on treatment.5,10 This is needed to identify a possible contraindication to the treatment, as detailed in the product label.5,10 To assess kidney function, only the formula specified and recommended in the product label should be used.5,10 Kidney function estimation should be based on equations taking into consideration a patient’s sex, age and weight, as recommended in the label.5,10

Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, Boehringer Ingelheim operates globally with 142 affiliates and a total of more than 47,400 employees. The focus of the family-owned company, founded in 1885, is researching, developing, manufacturing and marketing new medications of high therapeutic value for human and veterinary medicine.

Taking social responsibility is an important element of the corporate culture at Boehringer Ingelheim. This includes worldwide involvement in social projects, such as the initiative "Making more Health" and caring for the employees. Respect, equal opportunities and reconciling career and family form the foundation of the mutual cooperation. In everything it does, the company focuses on environmental protection and sustainability.

In 2013, Boehringer Ingelheim achieved net sales of about 14.1 billion euros. R&D expenditure corresponds to 19.5% of its net sales.

Footnotes

*In Spain these indications are pending for price and reimbursement.
En España el precio y las condiciones de financiación de esta indicación se hallan pendientes de tramitación.

Referências

  1. Böhm M. et al. Favourable Effects of Dabigatran Etexilate versus Warfarin on renal function change over time in patients with atrial fibrillation: results from the RE-LY trial. Clinical Trial Update Hotline Session. ESC Congress 2014.Presented on 2 September 2014.
  2. Cohen E. et al. A longitudinal assessment of the natural rate of decline in renal function with age.. J Nephrol. 2014 March 19. Epub ahead of print.
  3. Chatrou ML, et al. Vascular calcification: the price to pay for anticoagulation therapy with vitamin K-antagonists. Blood Rev. 2012;26:155-66.
  4. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–95.
  5. Pradaxa® European Summary of Product Characteristics, 2014.
  6. Di Nisio M, et al. Direct thrombin inhibitors. N Engl J Med. 2005;353:1028–40.
  7. European Medicines Agency Press Release - 25 May 2012: EMA/337406/2012. European Medicines Agency updates patient and prescriber information for Pradaxa. http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2012/05/news_detail_001518.jsp&mid=WC0b01ac058004d5c1
  8. Last accessed: August 2014.
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  10. FDA Drug Safety Communication: FDA study of Medicare patients finds risks lower for stroke and death but higher for gastrointestinal bleeding with Pradaxa (dabigatran) compared to warfarin – 13 May 2014. http://www.fda.gov/drugs/drugsafety/ucm396470.htm Last accessed: August 2014
  11. PRADAXA® Prescribing Information, 2014.
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  15. 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.
  16. Eriksson BI. et al. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, doubleblind, non-inferiority trial. Thromb Haemost. 2011;105:721-9.
  17. 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. Thromb Haemost. 2007;5:2178–85.
  18. Schulman S. et al. Dabigatran versus warfarin in the Treatment of Acute Venous Thromboembolism. N Engl J Med. 2009;361:2342–52.
  19. Schulman S. et al. Treatment of Acute Venous Thromboembolism with Dabigatran or Warfarin and Pooled Analysis. Circulation published online before print December 16, 2013, doi:10.1161/ CIRCULATIONAHA.113.004450
  20. Schulman S. et al. Extended use of dabigatran, warfarin or placebo in venous thromboembolism. N Engl J Med. 2013;368:709–18.
  21. Internal calculations based on IMS Health monthly Dataview database – April 2014 Update.
  22. Stangier J. et al. Pharmacokinetic Profile of the Oral Direct Thrombin Inhibitor Dabigatran Etexilate in Healthy Volunteers and Patients Undergoing Total Hip Replacement. J Clin Pharmacol. 2005;45:555–63.