Alan S. Go
Compared with warfarin, dabigatran was associated with similar incidence of ischemic stroke and overall bleeding in patients with atrial fibrillation, according to data published in Annals of Internal Medicine.
“After initial use of dabigatran in practice, published articles and reports to the FDA suggested major bleeding associated with dabigatran,” Alan S. Go, MD, director of the comprehensive clinical research unit at Kaiser Permanente Northern California, associate professor in the departments of epidemiology, biostatistics, and medicine at UCSF and consulting professor of health research and policy at Stanford University, and colleagues wrote. “In response, the FDA did preliminary analyses of bleeding risk using data from its Sentinel network, where no increased bleeding rates were seen with dabigatran versus warfarin, but adjustment for confounders was limited.”
Researchers evaluated the incidence of stroke, bleeding and myocardial infarction in patients with atrial fibrillation (AF) receiving dabigatran compared with warfarin. They performed a retrospective analysis of adults in the FDA Sentinel network aged 21 years or older who initiated therapy between November 2010 and May 2014. Using hospital claims among propensity score-matched patients starting dabigatran or warfarin treatment, Go and colleagues measured incidence of ischemic stroke, intracranial hemorrhage, extracranial bleeding and myocardial infarction.
In total, 25,289 patients began dabigatran therapy and 25,289 propensity score–matched patients began warfarin therapy between November 2010 and May 2014. Analysis showed that receiving dabigatran did not have significantly different rates of ischemic stroke (0.8 vs. 0.94 events per 100 person-years; HR =0.92; 95% CI, 0.65-1.28) or extracranial hemorrhage (2.12 vs. 2.63 events per 100 person-years; HR = 0.89; 95% CI, 0.72-1.09) compared with warfarin. Patients receiving dabigatran were less likely to have intracranial bleeding (0.39 vs. 0.77 events per 100 person-years; HR = 0.51; 95% CI, 0.33-0.79) and more likely to have myocardial infarction (0.77 vs. 0.43 events per 100 person-years; HR = 1.88; 95% CI, 1.22-2.9). The strength and significance of the link to dabigatran use and myocardial infarction differed in sensitivity analyses and by exposure definition (HR range, 1.13 to 1.43). Notably, older patients and patients with kidney disease experienced higher gastrointestinal bleeding rates with dabigatran than with warfarin.
“Collectively, these results provide reassurance about overall bleeding risks — particularly intracranial hemorrhage — associated with dabigatran use and give insights to potentially assist in decision making about stroke prevention strategies for certain patients with atrial fibrillation,” Go and colleagues wrote. “However, given the variability of findings for the outcome of myocardial infarction based on the analytic approach we used and results from other studies, the association between dabigatran and myocardial infarction remains uncertain.” – by Savannah Demko
Disclosures: Go reports grants from the FDA. Please see the study for all authors’ relevant financial disclosures.