A recent audit of bleeding events among patients taking Pradaxa (dabigatran) is the latest medical evidence that the risks of Pradaxa are serious, and should not be considered substantially similar to, or less than, the risks associated with competitor warfarin (brand name: Coumadin).
A group of hematologists in New Zealand, concerned by what they were witnessing in the short time Pradaxa had been available there (since July 1, 2011), sparked a review that was done in collaboration with the Haematology Society of Australia and New Zealand. The review was published online on February 1, 2012 at the Journal of the American College of Cardiology. The review panel identified 78 bleeding episodes over the two-month review period, including 44 cases handled by the panelists. Of the 44 cases with which the panelists were intimately familiar, 12 were severe.
One of the major factors in these bleeding episodes, according to the panelists, is prescriber error. Those errors include prescribing Pradaxa for patients with impaired renal function, which is also identified as another of the four major factors contributing to the episodes. Impaired renal function makes it difficult for the body to clear the active, blood-thinning agents from the body, which increases the chance that a bleed will become severe. In the RE-LY trial, which serves as the basis for the FDA approval of Pradaxa and the label information, less than 20% of the participants had impaired renal function, while 58% of the New Zealand review population had at least moderate renal impairment.
A third factor identified by the panelists is patient age. While the average age in the RE-LY trial was 71 years of age, and less than one-third of the RE-LY participants were more than 80 years of age. Among the population reviewed by the panelists, more than two-thirds of the patients were over 80 years old. This is significant because moderate renal impairment is reported in half of all patients with atrial fibrillation (the chief indication for Pradaxa) who are over the age of 80, and as discussed above, renal impairment increases the chance that a bleed will become severe.
The fourth factor identified by the panelists is complication arising from the lack of a reversal agent. If a patient being treated with warfarin begins to bleed, doctors can administer agents designed to counter-act warfarin, allowing the blood to clot and reducing the risk that the bleed will continue. No such reversal agent exists with Pradaxa. Doctors are not able to reverse its effects once a bleed is identified. This complication is compounded in patients who suffer from impaired renal function; in such a patient, it may be days before the body can cleanse itself from Pradaxa and allow the body's natural clotting function to resume. Of course, many of these patients won't have the days required for the clearance to occur.
Because the population reviewed in New Zealand has demographic properties different from the population studied in the RE-LY trial, the panelists encourage post-marketing surveillance and adverse-event reporting, and they encourage those that prescribe Pradaxa to change risk-benefit discussions with their patients in light of these new post-marketing reports, especially in patients over 80 or with impaired renal function.
Written in Collaboration with John M. Restaino, DPM, JD, MPH
Source: Feasibility and Safety of Dabigatran Versus Warfarin for Periprocedural Anticoagulation in Patients Undergoing Radiofrequency Ablation for Atrial Fibrillation: Results from a Multicenter Prospective Registry, J.Am.Coll. Cardiol. published online February 1, 2012.