1. In this population-based cohort study, apixaban was associated with a lower risk of gastrointestinal bleeding (GIB) as compared to dabigatran, edoxaban, or rivaroxaban.

2. Apixaban was associated with a lower risk of GIB for patients with chronic kidney disease or over 80 years old compared to dabigatran, edoxaban, or rivaroxaban.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Current guidelines recommend direct oral anticoagulants (DOACs) for stroke prevention in patients with atrial fibrillation due to a superior safety and similar efficacy profile compared to warfarin. However, there are no clear guidelines or clinical trials on how to choose between the most common forms of DOACs: apixaban, dabigatran, edoxaban, and rivaroxaban. In this population-based cohort study, the safety profile of apixaban, dabigatran, edoxaban, and rivaroxaban for patients with atrial fibrillation were compared using five electronic health databases from four countries. The primary outcomes were ischemic stroke or systemic embolism, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), and all-cause mortality. The median follow-up ranged from 534 to 1,612 days, depending on the DOAC and database origin. Apixaban was associated with lower GIB risk than all other DOACs. In patients who received a reduced dose of a DOAC, the incidence of ischemia stroke or systemic embolism was lower with apixaban than rivaroxaban and lower with dabigatran than rivaroxaban. For patients with chronic kidney disease, the risk for GIB was lower with apixaban than with dabigatran or rivaroxaban. In patients over 80 years old, apixaban was associated with lower GIB risk compared to any other DOACs. As a limitation, the study could not assess whether DOACs were prescribed consistently with labeling or severity of bleeding events. Additionally, observational studies are unable to rule out possibilities of confounding.

Click to read the study in AIM

In-Depth [retrospective cohort]: In this retrospective cohort study, the effectiveness and safety of four DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban) for patients with atrial fibrillation were evaluated using data from five multinational electronic health databases. The patient cohort (n=505,566) consisted of patients over 18 years old with atrial fibrillation. The median follow-up ranged from 534 to 1,612 days, depending on the DOAC and database origin. The primary outcomes were the incidences of ischemic stroke and systemic embolism, ICH, GIB, and all-cause mortality. To reduce bias, the analysis was conducted with the intention-to-treat approach. A lower risk of GIB was seen in the apixaban group compared to dabigatran (Hazard Ratio [HR]; 0.81, 95% Confidence Interval [CI], 0.70 to 0.94), rivaroxaban (HR, 0.75; 95% CI 0.66 to 0.79), and edoxaban (HR, 0.77; 95% CI, 0.66 to 0.91). Stratifying for patients who received a reduced dose of a DOAC, rates of ischemia stroke and systemic embolism were lower with dabigatran than with rivaroxaban (HR, 0.67; 95% CI, 0.49 to 0.94). A low dose of apixaban was also associated with a lower risk of GIB than a low dose of rivaroxaban (HR, 0.68; 95% CI, 0.61 to 0.77). For patients with chronic kidney disease, the risk for GIB was lower with apixaban compared to dabigatran (HR, 0.71; 95% CI, 0.54 to 0.94) or rivaroxaban (HR, 0.68; 95% CI, 0.59 to 0.77) in the propensity score matching method. In patients over 80 years old, the risk for GIB was lower with apixaban than dabigatran (HR, 0.65; 95% CI, 0.44 to 0.95), rivaroxaban (HR, 0.64; 95% CI, 0.57 to 0.72), and edoxaban (HR, 0.64; 95% CI, 0.50 to 0.82). No other comparisons of outcomes were significant. This study showed that apixaban may be preferable to other DOACs due to a lower risk of GIB and similar risks of stroke and ICH.

Image: PD

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