The trouble with dabigatran

Options for stroke prevention in high risk non-valvular atrial fibrillation have recently broadened with the addition of new oral anticoagulants as an alternative to warfarin, the traditional and effective treatment. The new class of drug promised safety and effectiveness without the monitoring and dose adjustment needed for warfarin. However, recent insights into the development and approval of dabigatran—the first new oral anticoagulant brought to market—have raised serious questions about its risks.1 New analysis published in The BMJ today illuminates a lack of transparency about the safety of unmonitored dabigatran, compounded by the drug’s fickle pharmacokinetics, which can cause a fivefold variation of plasma concentration.2 3

Equally unsettling are data integrity issues, which prompted the US Food and Drug Administration initially to refuse to review dabigatran. The investigators reviewed the data and identified 81 new events, including one stroke, one systemic embolism, and 69 major haemorrhages.4 An accelerated FDA review process also contributed to a less robust evaluation of risks and benefits. In effect, the current situation leaves clinicians and patients the choice between the devil they know and the one they don’t.

The …