Pradaxa is a novel oral anticoagulant designed to reduce the risk of stroke in patients with atrial fibrillation. From the day it was approved for sale in the United States an unprecedented number of serious adverse events and deaths attributed to the drug that were reported to the FDA. In response, the FDA launched an investigation into the safety of Pradaxa announcing that “the FDA is working to determine whether the reports of bleeding in patients taking Pradaxa are occurring more commonly than would be expected…” Less than a year later, in November 2012, the FDA concluded that “bleeding rates associated with new use of Pradaxa do not appear to be higher than bleeding rates associated with new use of warfarin.” The FDA based their conclusion on an analysis of data from FDA’s Mini-Sentinel pilot of the Sentinel Initiative. The approach utilized by the FDA was immediately criticized by health care professionals as “problematic” and described the conclusions reached by the FDA as “tantamount to a guess.” It appears the FDA did nothing more than ineffectively attempt to provide itself political cover for approving such an unsafe drug.
The problem with Pradaxa, and its hasty approval, lies in the fact that, unlike warfarin – the drug it is compared to in both its clinical trials and television advertisements – is that it cannot be reversed. Or to put another way, it has no antidote. When a warfarin patient experiences a bleeding event or is in need of emergency surgery, health care providers have a host of options available to them to reverse the blood thinning effects of warfarin and stop or slow the bleeding event or allow for safe surgical invention. Pradaxa has no such reversal agent or antidote. What does this mean in the real world use of Pradaxa? Are more Pradaxa patients bleeding to death than warfarin patients as a result of this lack of antidote? If you look to the pivotal clinical trial, the Randomized Evaluation of Long-Term Anticoagulation Therapy (“RE-LY”) you won’t find the answer. It’s a pretty simple question. Did more patients bleed to death on Pradaxa than they did on warfarin?
More than five years since the RE-LY trial was completed and more than two years since Pradaxa was approved, we are only just now beginning to answer this question. Rather than provide an answer to this important question in the original analysis and publication of RE-LY, the makers of Pradaxa waited until December 2012, after hundreds of lawsuits had been filed on behalf of Pradaxa patients who suffered a major or fatal bleed, and released data at a medical conference in a poster abstract. Amazingly, their “new” analysis of five-year-old data showed that Pradaxa patients were 44% less likely to die as a result of a major bleed than warfarin patients. Amazing in that if this were true, why not include it in the original analysis and publication? Perhaps the answer lies in the fact that poster abstracts are not peer-reviewed or subjected to scientific or regulatory scrutiny.
Less than a month after these “amazing” results were released by the makers of Pradaxa, on January 9, 2013, the Institute for Safe Medication Practice (“ISMP”), an independent research organization, published their own analysis of this very same question: are more patients bleedings to death on Pradaxa than warfarin? Amazingly, the ISMP reached a radically different answer than the makers of Pradaxa. ISMP determined that “reported [Pradaxa] bleeds were about 5 times more likely than warfarin to result in death…” 500% more likely to die as a result of a major bleed if you are on Pradaxa instead of warfarin. This really shouldn’t come as a surprise based on what we know about the availability of a reversal agent for these two drugs. What is surprising is the total disconnect between these two studies that reportedly addressed the same question.
Simply put: One of these two new studies got it wrong. Way wrong. Is this a matter of sloppy science or perhaps is this a deliberate effort by someone, for whatever rea$on, to mislead prescribers and users of Pradaxa? Only time will tell. Stay tuned.
Neil E. “Ned” McWilliams, Jr. is a partner with Levin Papantonio. His focus is on pharmaceutical and mass tort litigation.
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