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

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

“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

References

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