BMJ investigation claims safety info about dabigatran withheld by manufacturer

The makers of dabigatran allegedly failed to share information with regulators that would make using the drug safer—specifically, that monitoring plasma levels of the drug and adjusting doses accordingly could significantly reduce major bleeding, a new BMJ investigation found.

An investigator used previously confidential company documents (later released in a lawsuit) from dabigatran manufacturer Boehringer Ingelheim (BI) in her investigation. From the start, she noted, dabigatran has been marketed as a more convenient anticoagulant for stroke prevention in non-valvular atrial fibrillation patients because, unlike warfarin, it is taken in a fixed-dose regimen and doesn't need to be monitored or titrated.

However, she continued, internal company documents show that dabigatran monitoring and dose adjustment could reduce major bleeding by 30-40% compared with well-controlled warfarin, without affecting stroke risk—information that wasn't shared with regulators or physicians. The article was published online by BMJ on July 23.

A BI employee email about monitoring dabigatran plasma levels that was released during litigation said “This may not be a onetime test and could result in a more complex message (regular monitoring) and a weaker value proposition,” the BMJ investigator wrote. She also reported the company's response to her findings, which was to reiterate that dabigatran doesn't need to be monitored, that the company didn't share the information in question with regulators because it didn't provide “a reliable prediction of patient outcomes”, and that the FDA's own post-marketing analysis concluded that dabigatran's bleeding rates don't seem to be higher than warfarin's.

BMJeditorialists noted the investigation raised “serious questions” about the risks of dabigatran and that data integrity issues surrounding the drug are “equally unsettling.” They advised doctors to share decisions on anticoagulation with patients, taking into account “tolerance of unknown risks … of routine laboratory monitoring and dose adjustment, and their risk of stroke ….Patients and doctors tolerant of unknown risk and close monitoring will have to choose which drives them more strongly, with the more conservative option being warfarin,” they wrote.