Compared with other direct oral anticoagulants (DOACs), apixaban was associated with lower rates of GI bleeding but similar rates of ischemic stroke, intracranial hemorrhage, and all-cause mortality, a study found.
Researchers studied more than 500,000 new DOAC users in France, Germany, the United Kingdom, and the United States to compare outcomes and adverse effects of DOAC therapy. They analyzed data for 281,320 apixaban users, 61,008 dabigatran users, 12,722 edoxaban users, and 172,176 rivaroxaban users. Results were published by Annals of Internal Medicine on Nov. 1.
A total of 841 intracranial hemorrhages, 8,319 GI bleeding events, and 1,476 deaths occurred. Apixaban use was associated with lower risk for GI bleeding than use of dabigatran (hazard ratio [HR], 0.81; 95% CI, 0.70 to 0.94), edoxaban (HR, 0.77; 95% CI, 0.66 to 0.9), or rivaroxaban (HR, 0.72; 95% CI, 0.66 to 0.79). No substantial differences were observed for other outcomes or other DOAC-to-DOAC comparisons.
The results were consistent for the 101,397 patients ages 80 years or older, of whom 67,734 received apixaban, 3,609 received dabigatran, 4,292 received edoxaban, and 25,762 received rivaroxaban). In this group, apixaban use was associated with lower risk for GI bleeding than use of dabigatran (HR, 0.65; 95% CI, 0.44 to 0.95), rivaroxaban (HR, 0.64; 95% CI, 0.57 to 0.72), or edoxaban (HR, 0.64; 95% CI, 0.50 to 0.82).
Consistent associations between lower GI bleeding risk and apixaban versus rivaroxaban were observed both among patients receiving the standard dose (HR, 0.72; 95% CI, 0.64 to 0.82) and among those receiving a reduced dose (HR, 0.68; 95% CI, 0.61 to 0.77). Among patients who received a reduced dose, rates of ischemic stroke or systemic embolism were lower with apixaban than rivaroxaban (HR, 0.68; 95% CI, 0.46 to 1.01) and lower with dabigatran than rivaroxaban (HR, 0.67; 95% CI, 0.49 to 0.94). These associations were not found among patients who were prescribed standard-dose DOACs.
When researchers analyzed the subgroup of those with chronic kidney disease (n=71,430, of whom 47,046 received apixaban, 4,627 dabigatran, 1,180 edoxaban, and 18,577 rivaroxaban), the risks for ischemic stroke or systemic embolism, intracranial hemorrhage, and all-cause mortality were similar among the DOACs. Risk for GI bleeding was lower with apixaban than with dabigatran (HR, 0.71; 95% CI, 0.54 to 0.94) and lower with apixaban than with rivaroxaban (HR, 0.68; 95% CI, 0.59 to 0.77) in the propensity score-stratified cohorts.
According to the study authors, their results indicate that apixaban might be preferable to other DOACs because of the lower rate of GI bleeding and similar rates of stroke and intracranial hemorrhage. However, they noted that consideration of all potential factors would be needed, such as the use of gastroprotective agents in patients with high risk for GI bleeding.
“Our findings might raise the question of whether the reduced dose of rivaroxaban is appropriate to maintain effective stroke prevention outside restrictive trial settings,” the authors wrote. “While we await the confirmation studies, we cautiously recommend monitoring patients carefully.”