Analysis

Dabigatran, bleeding, and the regulators

BMJ 2014; 349 doi: http://dx.doi.org/10.1136/bmj.g4517 (Published 23 July 2014) Cite this as: BMJ 2014;349:g4517
  1. Thomas J Moore, senior scientist1,
  2. Michael R Cohen, president 1,
  3. Donald R Mattison, chief medical officer23
  1. 1Institute for Safe Medication Practices, 200 Lakeside Drive, Suite 200, Horsham, PA 19044, USA
  2. 2Risk Sciences International, Ottawa, ON, Canada
  3. 3University of Ottawa, Ottawa
  1. Correspondence to: T J Moore tmoore{at}ismp.org

Thomas J Moore and colleagues highlight the differences in how US and European regulators managed the safety problems of the new anticoagulant dabigatran and ask both to think again and mandate plasma monitoring of dabigatran

Dabigatran was the first drug across the finish line in the global race to develop a new and better replacement for the five decade old anticoagulant warfarin. An important indication was long term treatment to reduce the risk of stroke in patients with non-valvular atrial fibrillation. This vulnerable older group, mostly over age 75, number many millions worldwide. The main risk of treating atrial fibrillation with warfarin is that inhibiting coagulation can also result in bleeding in the brain, eyes, intestines, and elsewhere. A major bleed after warfarin treatment could result in patients losing 20-30% of their blood supply before the bleeding was halted. However, the objective of treatment was also important: blood could pool and form clots in the fibrillating atrial primer pumps, and these clots could travel to the brain, lungs, or elsewhere, causing irreversible damage.

As regulators at the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) considered the benefits and risks of dabigatran in 2010, they knew, or should have known, that reducing risk of bleeding with anticoagulants deserved to be ranked as a patient safety issue of the first order. A study of cases of drug adverse effects seen in 58 emergency departments across the United States1 showed that warfarin accounted for more emergency hospital admissions in patients aged 65 or older than any other drug. Warfarin accounted for 33.3% of all hospital admissions from the emergency department for adverse drug effects; insulins were next with 13.9%.

The two agencies’ evaluation of dabigatran was a study in contrasts. The FDA pursued a policy making the new …

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