Apparently, I-phone users will have yet another app available to them. A hematologist in New Zealand has developed a smart phone application that helps doctors manage patients who are taking Pradaxa. The promo pieces for this new application note that Pradaxa is an “exciting oral direct thrombin inhibitor” and that there has been much “fanfare” over the fact that patients taking Pradaxa do not have “the need for frequent INR monitoring, unlike warfarin.” Reportedly, the application was designed in order to give physicians more confidence in prescribing Pradaxa and tackling the challenge of reversing the anticoagulation properties of Pradaxa (in other words, the lack of a reversal agent or antidote for dabigatran which has led to hundreds if not thousands of avoidable deaths). It is interesting that the new application includes a number of questions geared towards identifying patients for whom Pradaxa use may be ill-advised, including patients with renal insufficiency, those over 75 years of age, as well as patients who have a history or risk factors for the development of GI bleeds or other bleeding events. This is information that has been poorly communicated by the drug’s manufacturer, and, if properly communicated, might have spared lives and avoidable harm to patients. The application also provides some hints for medical personnel who are trying to manage severe bleeding episodes (including manual compression, surgery, hemodialysis, and transfusion) as well as minor bleeding episodes (including administration of tranexamic acid – an antifibrinolytic agent that blocks the action of plasmin) in patients taking Pradaxa. It is doubtful that an IPhone application alone will lead to fewer deaths as a result of ingesting Pradaxa, but any tool that provides better information to doctors regarding those patients for whom Pradaxa use is inappropriate as well as tips on managing life-threatening bleeds caused by the drug is welcome (and long overdue).
On April 18, 2012, Boehringer issued press releases touting yet another analysis of the results from RE-LY, the clinical trial that constitutes most of the data submitted to the FDA prior to approval of Pradaxa. The reliability and limitations of the RE-LY trial will be one of the primary focuses of the emerging litigation efforts against Boehringer Ingelheim in the United States. This latest press release summarizes data relating to 153 patients of the 18,113 study participants. These 153 patients developed fatal or traumatic intracranial hemorrhage while taking Pradaxa. One of the authors of the study from McMaster University in Canada was quoted as claiming that patients on Pradaxa had a 70% lower risk of developing intracranial bleeding than patients taking warfarin. The study also noted that the patients who experienced bleeding in their brains were older than the average age of study participants, were more likely to have had a history of stroke or TIA in the past, and had greater impairment of their kidneys than others in the study. At this time, there are very few independent studies that have been published to provide a more critical evaluation of the claimed efficacy of Pradaxa as well as further evaluation of the unique safety risks associated with dabigatran.
On April 24, 2012, Boehringer announced a new global initiative to “broaden understanding of atrial fibrillation (AF) treatment” and, presumably, to broaden the number of patients for whom its beleaguered Pradaxa might be prescribed. The manufacturer’s press release noted that its Gloria-AF Registry will enroll up to 56,000 patients from 2,200 sites in 50 countries in order to assess the treatments and therapies given to those patients for their atrial fibrillation, including warfarin or Coumadin, acetylsalicylic acid, and Pradaxa. The press releases fail to indicate whether the AF Registry will help physicians to better identify the large number of patients, such as those with pre-existing kidney disease, a history of ulcers or GI bleeds, or the elderly, for whom therapy with Pradaxa is likely inappropriate.
The financial press was buzzing last week regarding Boehringer’s 2011 financial reports that showed a 6.2% increase in sales. The most striking (and troubling) aspect of the report was the fact that 77% of the increase in Boehringer’s total net sales was attributable to brisk sales of Pradaxa. International sales of Pradaxa topped more than $1 billion last year, which is the sales threshold above which a drug attains “blockbuster” status. This is truly a meteoric rise, as Pradaxa has only been approved in the United States for less than two years. The most interesting financial information will be for 2012, as many believe that the sales of Pradaxa will fall precipitously as more governmental drug regulators delve deeper into reports of an increased incidence of deaths and serious injuries relating to Pradaxa-induced bleeding episodes and the lack of a reversal agent for patients who suffer trauma or require emergency surgery. Once patients are given better information about the true risk profile of the drug, it is likely that fewer will choose to take Pradaxa. After interviewing many Pradaxa victims and their families, I can report that patients have not been given adequate information about the risks versus the benefits, and the convenience factor of the drug has been aggressively over-promoted. Sadly, the glowing press releases and articles from financial analysts gave short shrift to the more than 3,000 adverse event reports that the FDA received in the last quarter of 2011 for Pradaxa. These 3,000 reports would include 459 patient deaths and 1,331 who were hospitalized due to serious Pradaxa-induced conditions.