Dabigatran etexilate (Pradaxa®) associated with significantly lower rates of fatal and traumatic intracranial haemorrhage compared with Warfarin

Posted: 18 April 2012 | | No comments yet

A new analysis of the 18,113 patient…

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A new analysis of the 18,113 patient, RE-LY® trial highlights significantly lower rates of both fatal and traumatic intracranial haemorrhage (ICH) in patients treated with dabigatran etexilate (Pradaxa®) 110mg and 150mg bid compared to those treated with well-controlled warfarin. 1 As part of the primary safety endpoint, the analysis evaluated 154 intracranial haemorrhages that occurred in153 patients during the trial, including bleeding sites, rates, risk factors, associated trauma, and outcomes. Results of this safety analysis were recently published online in Stroke: The Journal of the American Heart Association.

Intracranial haemorrhage is mostly seen in older patients with atrial fibrillation (AF), and is one of the most devastating complications of anticoagulation therapy. Intracranial haemorrhage, which comprises intracerebral haemorrhage, subdural haematoma and subarachnoid haemorrhage, 1 is responsible for the majority of disability and death from bleeding related to treatment with the long time standard of care warfarin. 2

In the RE-LY® trial, Pradaxa® 110mg bid and Pradaxa® 150mg significantly reduced the rate of ICH by 70% and 59% respectively, compared to well-controlled warfarin. 3,4 This new detailed analysis of 154 intracranial haemorrhages across treatment groups in the RE-LY® trial showed:

  • Pradaxa® 110mg bid and 150mg bid were both associated with significantly fewer fatal (110mg: 11 vs. 32, P<0.001 / 150mg: 13 vs. 32, P<0.001) ICH events compared to well-controlled warfarin 1
  • In a combined analysis, Pradaxa® 110mg & 150mg bid were associated with significantly fewer traumatic (11 vs. 24, P<0.05) ICH events compared to well-controlled warfarin 1
  • When ICH did occur, the prognosis was similar across all treatment groups 1
  • In an historic comparison, the rates of ICH seen with both doses of Pradaxa® in RE-LY were similarly low as the rate seen in patients with AF receiving antiplatelet therapy. 1,5

“The risk of intracranial haemorrhage is a key factor when healthcare professionals are reviewing the benefit-risk profile of anticoagulation therapy, and this analysis highlights that both dosing regimens of Pradaxa® are safer than warfarin in this respect,” said Hans-Christoph Diener, M.D., Ph.D., Professor and Chairman, Department of Neurology, University Duisburg-Essen, Germany.

Dr. Stuart Connolly, Director, Division of Cardiology at McMaster University and member of The Population Health Research Institute, Hamilton, Ontario commented, “Intracranial haemorrhage is one of the most feared complications of anticoagulation therapy. In our hospital, we see patients frequently presenting with intracranial haemorrhage as a result of warfarin and unfortunately, this complication is associated with a high mortality rate. These data show us that not only is Pradaxa® associated with lower rates of intracranial haemorrhage overall, but that fatal and traumatic intracranial bleeding is also reduced, highlighting the favourable safety profile of Pradaxa®.”

The analysis showed that in RE-LY®, patients who experienced an ICH were, on average, older (mean age 75 [with ICH] vs. 71.5 [without ICH] P<0.001), associated with a higher frequency of previous history of stroke or TIA (P=0.001), used aspirin concomitantly more often (P=0.001), and had lower estimated creatinine clearance levels (P<0.001) compared with other study participants. 1 Differences were consistent across treatment arms. 1 A history of falling was not an independent risk factor for ICH amongst patients in the RE-LY® trial. 1

In the landmark RE-LY® trial, Pradaxa® 150mg bid significantly reduced the risk of stroke and systemic embolism by 35% compared to well-controlled warfarin (median time in therapeutic range (TTR) 67% 6), providing significantly superior stroke prevention in non-valvular atrial fibrillation (AF). 3,4 Pradaxa 110mg bid was shown to be non-inferior to well-controlled warfarin for the prevention of stroke and systemic embolism in patients with non-valvular AF. Pradaxa® 150mg bid is the only novel oral anticoagulant shown to significantly reduce both ischaemic and haemorrhagic stroke in patients with non-valvular AF compared to well-controlled warfarin. 3,4

RE-LY® was 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


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