NEJM Claims Pradaxa Adverse Events Due to Hyper-vigilant Reporting

This report is confusing to the many people who know from experience that taking the anticoagulant Pradaxa (dabigatran) is more dangerous than warfarin (Coumadin), the treatment that’s been the standard of care for decades.

According to a published perspective in the online March 14, New England Journal of Medicine (NEJM), the concern over Pradaxa may be due to heightened vigilance and “stimulated reporting” and not because there are more patients injured by the drug when compared to other anticoagulants.

The perspective article is authored by researchers within the FDA’s Center for Drug Evaluation and Research (CDER).

It flies in the face of adverse event reports (FAERS) coming into the FDA that claim Pradaxa users experienced excessive and uncontrolled cerebral, rectal and gastrointestinal bleeding have resulted in over 500 deaths.

It also conflicts with the findings of the Institute for Safe Medication Practices (ISMP), a nonprofit that monitors drug safety. According to the group, Pradaxa is at the top of the list of over 800 medication complaints the group monitors.  And ISMP reported earlier this year that Pradaxa users were five times more likely than warfarin users to have a fatal outcome.

This is the same division within the FDA that approved Pradaxa (dabigatran) in late 2010 as a more convenient alternative to the 1954-approved warfarin to treat the risk of stroke in patients with nonvalvular atrial fibrillation, that is AF not caused by heart valve problems.

They used the RE-LY trial (Randomized Evaluation of Long-term Anticoagulation Therapy) as a basis for the FDA approval. The RE-LY trial found no difference in the cases of excessive and uncontrolled bleeding when comparing Pradaxa to warfarin. The FDA also looked at insurance records and its own internal data to come to that conclusion.

What any report on adverse drug events should consider is the degree to which the drug maker takes advantage of a waiver to submit to the agency any report about an adverse event that the drug maker considers “not serious.” How might these waivers affect the unreliability of the data gathered?

The heightened vigilance concerning Pradaxa does not extend to the drug’s warning. Many patients and their doctors still do not understand there is no reversal agent to this anticoagulant as there is with warfarin. The only treatment is dialysis which is not a practical solution if you are bleeding to death. And, that is the real danger for people who urgently require reversal and bleed out because no agent is available to accomplish reversal of the anticoagulant effects of Pradaxa.

Yet the FDA continues to defend releasing Pradaxa with no antidote.

Meanwhile the manufacturer, Boehringer Ingelheim, plans to continue looking for a reversal agent and the FDA plans to continue postmarket surveillance of Pradaxa.