Last month, the FDA announced it is continuing to monitor patients taking Pradaxa as the result of reports of serious and even fatal bleeding events. In fact, Boehringer Ingeleheim, the manufacturer of Pradaxa, acknowledged 260 deaths as a result of bleeding. Although the FDA has not yet issued enhanced warnings, the European Medicines Agency (EMA) recommended updated product information for Pradaxa regarding the bleeding risk, and the FDA asked for users to report complications so that further studies could be done.
In addition to the increased risk of bleeding, there may also be an increased risk of heart attack for users of Pradaxa. According to a Cleveland Clinic study evaluating the risk of acute coronary events, Pradaxa was associated with a greater occurrence of myocardial infarction (MI) or acute coronary syndrome when compared to other similar treatments such as warfarin, enoxaparin or a placebo.
The Cleveland Clinic information comes not from a single study, but from seven separate randomized controlled trials that included 30,514 patients, and no one of which included more than 3,500 patients. Furthermore, the patients were studied for six months or less in each of the studies. The authors of the Cleveland Clinic study could not explain the higher risk of a heart attack with Pradaxa (dabigatran) use. It may have been an issue with Pradaxa, but the authors suggest that it is possible that warfarin and the other drugs are possibly just better at preventing MI.
Boehringer Ingleheim does not agree with the Cleveland Clinic analysis and points to the original RE-LY trial which, it claims, found that the increased risk of heart attack was not statistically significant.
Although the RE-LY trial included more than 18,000 patients for more than two years, it is difficult to ignore the obvious large profit incentive involved. The RE-LY trial, which concluded that Pradaxa offers patients a therapeutic simplification, was funded by Boeheringer Ingelheim, which is predicted to earn $1.3 billion in sales of Pradaxa by 2018.
There are issues with both studies, and more complete studies are needed to assess the safety of Pradaxa.
In an editorial accompanying the Cleveland Clinic analysis released in the Archives of Internal Medicine yesterday, Jeremy Jacobs, MBBS, and Jochanan Stessman, MD of Hadassah-Hebrew University Medical Center in Jerusalem, wrote,
Uchino and Hernandez (the authors of the Cleveland Clinic Study) suggest that physicians step back for a moment, take their own pulse, and retain a critical view as a powerful new drug enters clinical use on a potentially massive scale…. The Robust finding that dabigatran is associated with increased rates of MI is alarming and emphasizes the need for continued critical appraisal of new drugs after phase III trials.