A Medical Journal Article About New Meta-Analysis Of Four Pradaxa Trials Shows More GI Bleeds With "New" Blood Thinner Pradaxa Vs. "Old" Warfarin Treatment
A report published online in November 2013 by the medical journal JAMA: Internal Medicine, "A comparison of results of the US Food and Drug Administration's Mini-Sentinel Program with randomized clinical trials: The case of gastrointestinal tract bleeding with dabigatran", raises more drug-safety issues for the still relatively new blood thinner Pradaxa, from Boehringer Ingelheim Pharmaceuticals.
The key findings from this Research Letter published November 18, 2013 (which will appear in a 2014 print edition of JAMA: Internal Medicine) are concisely set forth in this Heartwire article, "GI Bleeding on Dabigatran: Controversy Pits Meta-analysis vs Real-World Data":
Randomized trial evidence suggests that treatment with dabigatran etexilate (Pradaxa, Boehringer Ingelheim) raises the risk of gastrointestinal (GI) bleeding compared with treatment with warfarin, suggests a meta-analysis, with findings entirely opposite those of a recent analysis of dabigatran and warfarin use in the FDA Mini-Sentinel database by several employees of the agency....
In the new meta-analysis of four [Pradaxa (dabigatran)] trials with enough available GI-bleed data, the risk of such events was raised 41% (p<0.001) with the new oral direct thrombin inhibitor compared with the vintage vitamin-K antagonist. The risk increase persisted after dropping any one trial from the meta-analysis, including the RE-LY trial, which overwhelmingly contributed the most patients and events, according to the authors, led by Dr Ilke Sipahi (University Hospitals and Case Medical Center, Cleveland, OH).
The RE-LY trial is well known to have shown more GI bleeds with [Pradaxa (dabigatran)], while intracranial hemorrhage was more common with warfarin (p<0.001 for both differences).
The increased GI-bleed risk in the meta-analysis contrasts with the 54% risk reduction seen for [Pradaxa (dabigatran)] vs warfarin in the Mini-Sentinel data, taken from electronic health records routinely monitored by the FDA covering a 14-month period ending at the close of 2011. But that analysis, recently published in the New England Journal of Medicine and reported then by heartwire , didn't adjust for potential confounders....
Sipahi agreed that a "healthy-user bias," including a lesser prevalence of renal dysfunction, may underlie the apparent GI-bleeding risk reduction with [Pradaxa (dabigatran)] in the Mini-Sentinel analysis.
We will continue to monitor the medical journals for developments as regards the association between Pradaxa and gastrointestinal (GI) bleeding events, some of which have caused patient deaths.