A study of Medicare beneficiaries suggests that dabigatran (Pradaxa, Boehringer Ingelheim) should be prescribed with caution, especially among high risk patients, as it may be associated with a higher incidence of major bleeding and a higher risk of gastrointestinal bleeding, despite a lower risk of intracranial haemorrhage than warfarin, according to a study published online by JAMA Internal Medicine.
Dabigatran was approved by the US Food and Drug Administration (FDA) in 2010 to prevent stroke and embolism in patients with non-valvular atrial fibrillation based on the results of the RE-LY trial. The trial did not find a difference in major bleeding between dabigatran and warfarin, but dabigatran was better than warfarin at preventing a stroke. Since then, the FDA has recieved reports of severe dabigatran-related bleeding. It remains unclear whether the use of dabigatran leads to more bleeding compared to warfarin, according to background information provided in the article.
Inmaculada Hernandez (University of Pittsburgh, Pittsburgh, USA) and colleagues compared the risk of bleeding associated with dabigatran and warfarin by analysing Medicare data for patients newly diagnosed with atrial fibrillation from October 2010 to 2011. Patients were followed up until anticoagulant use was discontinued or switched, the patient died or until December 2011. The study included 1,302 dabigatran users and 8,102 warfarin users.
The study results indicate that the incidence of major bleeding was 9% for the dabigatran group and 5.9% for the warfarin group. The risk of intracranial haemorrhage was higher among warfarin users, but otherwise dabigatran was consistently associated with an increased risk of major bleeding and gastrointestinal haemorrhage for all the subgroups of high-risk patients analysed, including those 75 years or older, African Americans, those patients with chronic kidney disease and those with more than seven coexisting illnesses. The risk of major bleeding was especially high for African Americans and patients with chronic kidney disease.
“To the best of our knowledge, our study is the first to compare the safety profile of dabigatran and warfarin using a nationally representative sample of Medicare beneficiaries. We found that in the real-world clinical practice, after adjusting for patient clinical and demographic characteristics, dabigatran was associated with a higher incidence of major bleeding regardless of the anatomical site; in addition dabigatran was associated with a higher risk of gastrointestinal bleeding but a lower risk of intracranial haemorrhage than warfarin. Before more evidence is available, dabigatran should be prescribed with caution in high-risk patients,” the authors conclude.
In a related editor’s note, JAMA Internal Medicine editor-in-chief Rita F Redberg, of the University of California, San Francisco, writes: “Hernandez et al give us cause for concern because it appears that the bleeding risk for dabigatran is higher than for warfarin and significantly greater than originally appeared at the time of the FDA approval. These data conflict with the recent Mini-Sentinel analysis from the FDA. The authors note the FDA failed to adjust for differences in patient characteristics, which would bias the results. This study reminds us of the importance of post marketing data and of having adequate data on risks and benefits to advise our patients accurately.”
This study was supported by a grant from the Commonwealth Foundation and Agency for Healthcare Research and Quality.