Larger dose dabigatran offers benefits in elderly patients

Elderly patients given upper doses of the anticoagulant dabigatran had reduced risk for stroke, intracranial hemorrhage and mortality compared with warfarin, according to a study published online Oct. 30 in Circulation. However, dabigatran had an increased risk of major gastrointestinal bleeding.

Dabigatran (Pradaxa, Boehringer Ingleheim) is approved to reduce the risk of stroke and systemic embolization in patients with nonvalvular atrial fibrillation and acts as a direct thrombin inhibitor. The joint FDA and the Centers for Medicare & Medicaid Services (CMS) team noted that these outcomes were most pronounced in patients taking the 150 mg dose of dabigatran. The 75 mg dose appeared to reduce risk only for intracranial hemorrhage.

This study was part of the SafeRx Project run jointly by the FDA and CMS.

David J. Graham, MD, MPH, of the Center for Drug Evaluation and Research at the FDA in Silver Spring, Md., and colleagues reviewed Medicare patient claims data between 2010 and 2012. They included 67,494 and 273,920 dabigatran and warfarin treated patients, respectively. Cohorts were matched and follow-up began after the first anticoagulant prescription fill.

In the clinical practice setting, 150 mg of dabigatran had lower risk of stroke (hazard ratio 0.8), intracranial hemorrhage (hazard ratio 0.34), acute MI (hazard ratio: 0.92) or death (hazard ratio 0.86) compared with warfarin in elderly patients with nonvalvular atrial fibrillation. Risk for gastrointestinal bleeding, however, increased (hazard ratio 1.28), particularly in women 75 or older and in men 85 and older compared with warfarin.

In patients receiving 75 mg of dabigatran twice daily, outcomes were not significantly different from warfarin, except for intracranial hemorrhage risks in patients using dabigatran. The research team expressed concern that patients were being underdosed, as only 33 percent of patients in this review had a diagnosis of chronic kidney disease in the six months prior. Explicit coding for severe renal impairment occurred in only 20 percent of chronic kidney disease patients given the 75 mg dose.

They wrote underdosing “could explain why we found no difference in risk of ischemic stroke, major gastrointestinal bleeding or mortality between warfarin and the lower dose of dabigatran.” Previous trials suggested that 110 mg doses twice daily of dabigatran were less effective than 150 mg. These prior findings affected U.S.-approved marketing of dabigatran, Graham et al wrote.