Pradaxa® (dabigatran etexilate) 150mg bid provides consistent stroke reduction over warfarin in patients with atrial fibrillation taking antiplatelet

PARIS - Monday, August 29th 2011 [ME NewsWire]

(BUSINESS WIRE)-- For NON-U.S. & NON-UK Health Media Only

New data from two RE-LY® trial sub-group analyses show that dabigatran etexilate provides consistent benefits in stroke in atrial fibrillation (AF) compared to well-controlled warfarin, irrespective of whether patients use antiplatelet1 or other concomitant therapies, such as the anti-arrhythmics amiodarone or verapamil.2 The relative benefits of dabigatran etexilate over well-controlled warfarin in the overall results of RE-LY®3,4 were consistent across patients using these concomitant treatments.1,2 The data was presented at the European Society of Cardiology (ESC) Congress 2011, in Paris, France.

Dabigatran etexilate 150mg bid is the only novel oral anticoagulant approved for stroke prevention in AF shown superior to well-controlled warfarin (median TTR 67%5,6) in an intention to treat analysis.3,4 These groundbreaking results were demonstrated in RE-LY®, a PROBE trial (prospective, randomized, open-label with blinded endpoint evaluation), 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.3,7

The new findings are significant because the long time standard of care warfarin is known to interact with numerous medications, including many common co-medications metabolised via the Cytochtrome P450 pathway. In addition, approximately one in five patients with AF are being prescribed antiplatelet therapy alongside warfarin for conditions such as coronary artery disease, acute coronary syndrome, or recent coronary artery stenting.8 The safety of antiplatelet therapy in combination with anticoagulants has been a physician concern, with the combination shown to increase major bleeding over the use of anticoagulation alone.8

The present antiplatelet analysis assessed the combined use of aspirin and/ or clopidogrel in 8,507 patients taking either dabigatran etexilate (150mg bid or 110mg bid) or well-controlled warfarin.1 The second analysis evaluated interactions with dabigatran etexilate and the use of P-glycoprotein inhibitors* such as amiodarone, verapamil and diltiazem.2 Results showed:

As seen in the overall RE-LY® trial, dabigatran etexilate 150mg bid maintained its efficacy benefits over well-controlled warfarin for the prevention of stroke and systemic embolism (SEE) in AF patients using antiplatelet therapy (HR= 0.80, 95% CI=0.59-1.08), with similar rates of major bleeding events compared to warfarin (HR=0.93, 95% CI=0.76-1.12)1 and non-significant p-values for interaction indicating consistency of this sub-group compared to the overall RE-LY® trial
Dabigatran etexilate 110mg bid remained as effective as well-controlled warfarin in preventing stroke/SEE in patients with AF using antiplatelet therapy (HR=0.93, 95% CI=0.70-1.25, p-value for interaction = ns), with reduction in major bleeding events (HR=0.82, 95% CI=0.67-1.00; p-value for interaction = ns)1
Concomitant antiplatelet use increased the risk of major bleeding (HR=1.60, 95% CI=1.41-1.81) in all treatment arms, with no difference between patients treated with dabigatran etexilate or warfarin1
Use of P-glycoprotein inhibitors*, such as amiodarone, verapamil and diltiazem, in combination with dabigatran etexilate did not alter the overall benefits of dabigatran etexilate for stroke prevention, major bleeding or intracranial hemorrhage relative to well-controlled warfarin.2

Prof. Antonio Dans, Department of Medicine, University of the Philippines College of Medicine said, “Even though combining antiplatelets with an anticoagulant bears the risk of increased bleeding, it is often required for AF patients with coronary artery disease. The new results are thus an important findings for clinical practice, because they show that the benefits of dabigatran etexilate over warfarin for the prevention of stroke in AF remain unchanged when patients use concomitant antiplatelet therapy.”

Dabigatran etexilate was recently approved for stroke prevention in AF in the EU following previous approvals in the U.S., Canada, Japan, Australia and many other countries across five continents.6,9-12

~ENDS~

* P-glycoprotein inhibitors work to inhibit the P-glycoprotein transporter which is a membrane-associated protein that transports various substrates across cell membranes of the body, thereby affecting the bioavailability of drugs

Please click on the link below for ‘Notes to Editors’ and ‘References’:

http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2011/28_august_2011_dabigatran.html

Contacts

Boehringer Ingelheim GmbH

Dr. Reinhard Malin

Corporate Communications

Media + PR

Phone: + 49 - 6132 – 77 90815

Fax: + 49 - 6132 – 72 6601

E-mail: press@boehringer-ingelheim.com

Twitter: http://twitter.com/Boehringer

www.boehringer-ingelheim.de