The results of a long-term study on the side effects of blood-thinning drug Pradaxa indicated that about three percent of users will face at least one major bleeding event per year. Those taking the higher dose of 150 mg have a slightly higher risk.
Since the FDA approved Pradaxa in October 2010, the drug has been linked with a number of reports of life-threatening bleeding at levels higher than those expected from pre-approval clinical trials. Patients who have suffered serious injuries have filed lawsuits against manufacturer Boehringer Ingelheim, alleging the company failed to provide adequate warnings about the risks.
Extended Study on Side Effects of Pradaxa
Published in the journal Circulation, the RELY-ABLE study was an extension of the original RE-LY trial on Pradaxa, which the company used to establish the safety and effectiveness of the drug for FDA approval. The follow-up observed patients who continued to take Pradaxa for up to about two years after the initial trial was over.
A total of 5,851 patients were enrolled in the new study. Results showed that 3.74 percent of those who were taking Pradaxa at the 150 mg dose were likely to experience major hemorrhaging. Those taking the 110 mg dose had a 2.99 percent risk of a major bleeding event.
Mortality rates were about the same, with about 3.02 percent of those taking the 110 mg dying each year, and 3.1 percent taking the 150 mg dose passing away each year.
The authors stated, During 2.3 years continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily compared to 110 mg, and similar rates of stroke and death.
Study Questions FDA Conclusions
The FDA approved Pradaxa to help patients suffering from non-valvular atrial fibrillation reduce their risk of stroke. When the medication first came out in 2010, Boehringer Ingelheim touted it as being superior to warfarin, which for about 50 years has been the leading anticoagulant for reducing the risk of stroke. Unlike Warfarin, Pradaxa requires no regular blood monitoring and also requires no dietary modifications.
Yet post-marketing reports seemed to indicate that more patients suffered bleeding events with Pradaxa than with warfarin. In November 2012, however, the FDA issued a statement saying that bleeding rates associated with new use of Pradaxa do not appear to be higher than bleeding rates associated with new use of warfarin.
A later study, however, cast new doubts on the FDA’s conclusions. Researchers from University of Chicago presented research at the American College of Cardiology Scientific Sessions in March 2013 showing a high number of bleeding events in those taking Pradaxa compared to warfarin. After examining the reports of bleeding events submitted to the FDA between 2011 and 2012, the research team found that Pradaxa was the primary or secondary agent in over 4,000 bleeding events, with 638 fatalities. Warfarin, on the other hand, was associated with a little over 800 bleeding events, with 44 fatalities.
Experts Question Safety of Pradaxa
Meanwhile, some have questioned the validity of the original RE-LY study used to establish the safety of Pradaxa. Henry I. Bussey, Pharm. D., FCCP, FAHA, the safety and efficacy of Pradaxa is questionable while the use of the drug presents other potential risks, such as increased heart attack, other adverse effects, and the inability to reverse the effects of the drug. Bleeding associated with warfarin can be stopped with injections of vitamin K. Pradaxa has no such readily available antidote, making bleeding events much more dangerous and potentially fatal.
Dr. Brian F. Gage also questioned the results of RE-LY in an editorial published in the New England Journal of Medicine. There, he stated that heart attack and gastrointestinal side effects were significantly more common with Pradaxa than with warfarin.