Dabigatran Carries Risk of GI Bleeding; Risk Greater in Kidney Disease, Black Patients

Inmaculada Hernandez, PharmD PhD Student, Health Services Research and Policy Deparment of Health Policy and Management Graduate School of Public Health University of Pittsburgh Pittsburgh, PA 15261MedicalResearch.com Interview with:
Inmaculada Hernandez, PharmD

PhD Student, Health Services Research and Policy
Deparment of Health Policy and Management
Graduate School of Public Health
University of Pittsburgh Pittsburgh, PA 15261

Medical Research: What is the background for this study? What are the main findings?

Response: The approval of dabigatran was considered a major contribution to the therapeutic arsenal of anticoagulants since warfarin, whose therapeutic management is complicated, was the only oral anticoagulant approved before 2011. Clinicians therefore considered dabigatran a very promising drug; however, the safety warnings released by the regulatory agencies and the reports of bleeding published in 2011 raised concerns about the safety profile of dabigatran. By the time we initiated our study, the FDA had concluded that dabigatran was associated with similar rates of bleeding than warfarin. However, the results of this observational study were not adjusted by patient characteristics. We therefore compared the risks of bleeding with dabigatran and warfarin adjusting for patient characteristics and using propensity score methods to mitigate selection biases, which observational studies are sensitive to.

We found that dabigatran was associated with a higher risk of major bleeding and gastrointestinal bleeding than warfarin. However, the risk of intracranial bleeding was lower with dabigatran. In addition, we found that the increased risk of bleeding with dabigatran was specially higher for African Americans and for patients with chronic kidney disease.

Medical Research: What should clinicians and patients take away from your report?

Response: As we mention in the discussion section of our paper, the most important take-away points from our paper are:

  • First, dabigatran should be prescribed with caution, especially among Blacks and renal impaired patients. In other words, clinicians should not assume that bleeding risk is lower with dabigatran than warfarin because the therapeutic management is easier (i.e. it does not require INR monitoring and does not have as many interactions).
  • Second, it is important to explain patients how to detect gastrointestinal bleeding (i.e. check stool color), so that it can be stopped as promptly as possible.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: In the future, we would like to compare the incidence of bleeding with dabigatran and warfarin to other anticoagulants that recently became available (rivaroxaban and apixaban). In addition, it would be interesting to study whether prescribing patterns of dabigatran have changed over time as a result of the safety warnings released by the regulatory agencies and the publication of new evidence on the safety profile of dabigatran.

Citation:

Hernandez I, Baik S, Piñera A, Zhang Y. Risk of Bleeding With Dabigatran in Atrial Fibrillation.
JAMA Intern Med. 2015;175(1):18-24. doi:10.1001/jamainternmed.2014.5398.