Recently, global pharmaceutical giant Boehringer-Ingelheim (BI) posted a press release (dated 10 December 2012) on numerous sites on the World Wide Web, proclaiming triumphantly that
“Results from a new post-hoc analysis of the landmark RE-LY® trial show that in patients experiencing a major bleeding event, treatment with Pradaxa® (dabigatran etexilate) was associated with lower mortality and a shorter length of stay in intensive care compared to warfarin.”
A “post-hoc” (literally, “after this”) study is one in which results of an scientific experiment are examined long afterward, the objective being to find patterns that were not considered relevant at the time the experiment was first carried out. Such a study can be useful in ferreting out information that may originally have been overlooked and therefore might change some of outcomes. The process can also clarify results about which there may have been questions.
The results of the post hoc study was presented at the 54th Annual Meeting and Exposition of the American Society of Hematology on 8 December, 2012 in Atlanta, Georgia. The paper was presented by a board of distinguished professionals in the field of hematology, one of which was Dr. Martina Bruekmann, who is an employee of BI, and included Dr. Lars Wallentin, who worked on the original RE-LY study – and who himself has received institutional grants from BI. The RE-LY study was itself sponsored by BI. According to a letter issued by the Health Sciences Department at the University of British Columbia, the “comparison between warfarin and dabigatran was not blinded...outcomes are subject to performance and ascertainment bias favoring dabigatran.” Significantly, the U.S. Food and Drug Administration found a similar bias in the study. Furthermore, a meta study published in the Journal of the American Medical Association in April of 2012 found that the risks of Coumadin (warfarin, the standard treatment for stroke prevention) were not as high as the RE-LY study had suggested.
According to the abstract, the team analyzed the RE-LY study in terms of treatment and length of patient hospital stays in the wake of a hemorrhage in addition to comparisons of patients on Pradaxa and warfarin. One of the findings was that patients who were at greatest risk for potentially fatal hemorrhaging while taking Pradaxa were older and used anti-inflammatory medications (such as aspirin) on a more frequent basis. In addition, these patients had impaired renal function (the kidneys aren't doing so well in eliminating substances from the blood). Their conclusion:
“Prognosis after a major bleed on dabigatran was, despite lack of a specific antidote, better than with warfarin. There was also a shorter stay in intensive care with dabigatran compared to warfarin.”
At least they mentioned the lack of an antidote when they presented their paper at the conference. That fact was completely absent from BI's glowing press release.
It is also interesting that the press release is intended for “non-U.S., non-U.K. and non-Canadian media only.”
The timing is significant. As the number of lawsuits being filed against BI over injuries attributed to its flagship product continues to increase, a potentially major competitor to Pradaxa, known as Eliquis, has been approved by the European Medicines Agency. BI is also up against a deadline; Judge David Herndon, who is overseeing the multi-district litigation against the company, has given BI until Monday, 17 December, to prove that claims against its flagship product have no basis.
Agarwal, Shikhar MD, et. al. “Current Trial-Associated Outcomes With Warfarin in Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation: A Meta-analysis.” Journal of the American Medical Association, 23 April 2012.
Majeed, Ammar MD, et. al. “Management and Outcomes of Major Bleeding On Dabigatran or Warfarin.” Presented at the 54th ASH Annual Meeting and Exposition, 08 December 2012. Abstract available at https://ash.confex.com/ash/2012/webprogram/Paper49489.html.
N/A. “DrugRisk Center: Pradaxa Alternative Approved in Europe Amid Growing Lawsuits.” PRWire via RedOrbit, 07 December 2012. Available at: http://www.redorbit.com/news/science/1112744580/drugrisk-center-pradaxa-alternative-approved-in-europe-amid-growing-lawsuits/.
Boehringer-Ingelheim Press Release. “Treatment with Pradaxa® Associated With Better Patient Outcomes After a Major Bleeding Event Compared to Warfarin.” Via BusinessWire, 10 December 2012. Available at http://news.yahoo.com/treatment-pradaxa-associated-better-patient-102600278.html,
Wallentin, Lars MD et. al. “Efficacy and Safety of Dabigatran Compared to Warfarin at Different Levels of INR Control for Stroke Prevention in 18,113 Patients with Atrial Fibrillation in the RE-LY Trial” (RE-LY Study). Available at http://assets.cardiosource.com/Wallentin_RE-LY.pdf
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