Reykjavik, Iceland—With the introduction of direct oral anticoagulants (DOACs) about a decade ago, most studies have compared bleeding risks compared to warfarin, not among DOACs themselves. Recent research suggests, however, that rivaroxaban is associated with higher gastrointestinal bleeding (GIB) rates than apixaban and dabigatran regardless of treatment indication.
University of Iceland and Landspítali–The National University Hospital of Iceland reseachers point out that GIB rates for DOACs and warfarin “have been extensively compared. However, population-based studies comparing GIB rates among different DOACs are limited.”
To remedy that, the study team compared rates of GIB among apixaban, dabigatran, and rivaroxaban. Included in the nationwide population-based cohort study were Landspítali–The National University Hospital of Iceland and the four regional hospitals in Iceland. Results were published in Annals of Internal Medicine.
The focus was on patients who were new users of apixaban, dabigatran, and rivaroxaban from 2014 to 2019. Rates of GIB in 2,157 patients receiving apixaban, 494 patients receiving dabigatran, and 3,217 patients receiving rivaroxaban were compared.
Results indicate that for all patients, rivaroxaban had higher overall rates of GIB (3.2 vs. 2.5 events per 100 person-years; hazard ratio [HR], 1.42 [95% CI, 1.04-1.93]) and major GIB (1.9 vs. 1.4 events per 100 person-years; HR, 1.50 [CI, 1.00-2.24]) compared with apixaban.
In addition, rivaroxaban also had higher GIB rates than dabigatran, with similar point estimates, although the authors note that the CIs “were wider and included the possibility of a null effect.”
When only patients with atrial fibrillation were included, rivaroxaban was associated with higher rates of overall GIB than apixaban (HR, 1.40 [CI, 1.01-1.94]) or dabigatran (HR, 2.04 [CI, 1.17-3.55]), however. On the other hand, dabigatran was associated with lower rates of upper GIB than rivaroxaban in both analyses, the researchers state.
In another recent study, researchers from the Department of Pharmacy at the Veterans Affairs Greater Los Angeles Healthcare System and Western University of Health Sciences in Pomona, CA, determined that “DOACs overall, apixaban, and dabigatran, but not rivaroxaban, were associated with less total bleeding and death than warfarin in patients with heart failure and atrial fibrillation at all levels of renal function.”
In their report in Circulation: Cardiovascular Quality & Outcomes, the authors state, “Renal function decline resulted in increased bleeding in patients with DOACs. DOAC dose adjustment was often indicated, associated with increased bleeding when not adjusted, emphasizing the need for closer monitoring in these patients.”
The study team notes that patients with heart failure and atrial fibrillation are an important atrial fibrillation subgroup in which DOACs have not been adequately studied in real-world settings, adding, “Since DOACs rely on renal elimination and renal dysfunction is prevalent in patients with heart failure, their use may increase bleeding risk, negating some of their advantage over warfarin.”
The retrospective cohort study used linked Veterans Administration databases of patients with heart failure newly started on warfarin or DOACs for atrial fibrillation from October 2010 to August 2017. Outcomes for the participants, 23,?635 on warfarin and 25,?823 on DOACs, included time to first bleeding, stroke, and death using Cox proportional-hazards models with inverse probability of treatment weighting.
Total bleeding (HR, 0.62 [95% CI, 0.56-0.68]), major bleeding (HR, 0.49 [95% CI, 0.40-0.61]), and death (HR, 0.74 [95% CI, 0.71-0.78]) were lower with DOACs compared with warfarin, and with apixaban and dabigatran but not rivaroxaban, the researchers point out.
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