Friday, July 25, 2014

The Scandal of Dabigatran – A Summary

We’ve been desperate for a more elegant solution to anticoagulation than rat poison for seemingly an eternity.  Now, we have them: direct thrombin and factor Xa inhibitors.  The studies supporting their use seem favorable.

But, as the old story goes – and as previously reported on this blog many times – Boehringer Ingelheim has been selectively reporting only the most favorable aspects of their flagship drug, dabigatran.  Increased cardiovascular events have been downplayed through study design not powered to detect a difference.  Issues with fixed dose therapy – and lack of a range of options for patients with renal impairment – rear their ugly head in multiple case reports.

Then, the most damning – the recent legal action reveals Boehringer Ingelheim, after selling dabigatran as not requiring monitoring nor having a reliable assay to monitor its effects, was hiding information on both counts.  There is, in fact, substantial individual-patient variability in dabigatran efficacy and bleeding risk, and the HEMOCLOT test is, in fact, a reliable method of measuring activity.  Review of internal documents shows employees were aware many patients might benefit from routine monitoring of levels – but this would eliminate one of its selling points (and cost savings) over warfarin.  These e-mails also specifically address the potential damaging effect on sales if said information were released in the scientific literature.

Clearly, yet another case where first-mover status into a lucrative market trumped patient-safety concerns.  If you wonder where the rampant skepticism regarding conflict-of-interest comes from on this blog – this is a beautifully flagrant example.

“Dabigatran: how the drug company withheld important analyses”
http://www.bmj.com/content/349/bmj.g4670 (free fulltext)

Previous EM Lit of Note Posts:
Rivaroxaban Can Be Reversed, But Not Dabigatran” - Sept 2011
Scattering Tacks In The Road” - Jan 2012
Dabigatran — Uncharted Waters and Potential Harms” (Annals of Internal Medicine) - May 2012
Dabigatran - It's Everywhere!” - Sept 2012
Not-So Routine Surgery on Dabigatran” - Sept 2012
Dabigatran: Hidden Danger in the Home” - Nov 2012
Dabigatran & CES1 SNP rs2244613” - Mar 2013

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