Monday, March 18, 2013

Dabigatran Post-Marketing Data

Perspective is everything. Changing your perspective when learning can help gain a higher understanding; likewise in teaching, altering your perspective can help make a point. Take for, example, this recent article in NEJM[1] regarding the true incidence of bleeding associated with dabigatran.  Take a step back from the usual perspective of dabigatran being the spawn of Satan, if only for a moment.

In this article, the authors propose that the reported incidence of bleeding as a result of dabigatran is inflated from what would normally be reported. Going back to RE-LY, the overall incidence of bleeding was lower in patients taking dabigatran compared to warfarin.  When a higher than anticipated number of bleeding events were reported to the FDA adverse event reporting system, further investigation took place. These reports led the authors to conduct their own [albeit flawed] review of the FDA Mini-Sentinel database to find similar bleeding incidences, and note a larger phase II study is on the way. 

Part of the post-marketing safety data of new drugs comes from voluntary reporting systems like Medwatch.  Across the board there is a tendency to under-report adverse events because, well, it’s more work (unless you have pharmacy students looking board).  What seems to be going on with dabigatran and the inflation of adverse event reporting is thought to be a result of the Weber effect. In a nutshell, since everyone is on the bash-dabigatran bandwagon, there is an increased awareness, almost excitement, to report adverse events. When compared to warfarin, there seems to be underreporting of bleeding (I mean, we all see it on a daily basis).

Of course, when bleeding is discussed, several confounding patient factors do need to be considered. With dabigatran, bleeding incidence of bleeding has been linked to inappropriate use of the drug; i.e., normal dosing in patients with impaired renal function.   Not understanding the lack of pharmacokinetic data supporting the renal dosing recommendation is not a reflection of “real-world practice,” it’s poor medicine.  

The perspective I am trying to describe is similar to one I recently heard regarding tPA for AIS: let’s not look for patients with contraindications to tPA, but rather, ask which patients will benefit from tPA.  With dabigatran, lets be aware of the risks of bleeding and the difficulties in reversing the anticoagulant effects, but also identify patients who will benefit from dabigatran and not treat is as a carte blanche replacement for warfarin.

[1]Ross Southworth M, Reichman ME, Unger EF. Dabigatran and Postmarketing Reports of Bleeding. N Engl J Med. 2013 Mar 13

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