Apixaban linked to lower risk of serious bleeding compared to warfarin in patients with or without afib

A comparison of direct oral anticoagulants and warfarin found that apixaban had the lowest number needed to treat to avoid one extra major bleed compared to warfarin, while rivaroxaban had the lowest number needed to harm with death from bleeding.


A recent comparison of anticoagulants in a real-world population found apixaban to be the safest drug, with reduced risks of major, intracranial, and gastrointestinal bleeding compared to warfarin.

Using data from two U.K. primary care databases, researchers assessed the association between direct oral anticoagulants (DOACs) and the risks of bleeding and all-cause mortality compared with warfarin. The main outcome was major bleeding leading to hospital admission or death. Results were published online on July 4 by The BMJ.

Of study participants who started or restarted anticoagulants (after more than a 12-month gap) between 2011 and 2016, 103,270 (53%) had atrial fibrillation and 92,791 (47%) did not. Most were taking warfarin (n=132,231), while the remaining 63,830 participants were taking DOACs (rivaroxaban, n=37,863; apixaban, n=18,223; and dabigatran, n=7,744). Researchers adjusted analyses for demographic and clinical variables (e.g., sex, age, smoking status, comorbidities, and previous events).

In patients with atrial fibrillation, apixaban was associated with a decreased risk of major bleeding compared to warfarin (adjusted hazard ratio [HR], 0.66; 95% CI, 0.54 to 0.79) and intracranial bleeding (adjusted HR, 0.40; 95% CI, 0.25 to 0.64), while dabigatran was associated with a decreased risk of intracranial bleeding (adjusted HR, 0.45; 95% CI, 0.26 to 0.77). An increased risk of all-cause mortality was seen in patients taking rivaroxaban (adjusted HR, 1.19; 95% CI, 1.09 to 1.29) and in those on lower doses of apixaban (adjusted HR, 1.27; 95% CI, 1.12 to 1.45).

In patients without atrial fibrillation, apixaban was associated with a decreased risk of major bleeding (adjusted HR, 0.60; 95% CI, 0.46 to 0.79), any gastrointestinal bleeding (adjusted HR, 0.55; 95% CI, 0.37 to 0.83), and upper gastrointestinal bleeding (adjusted HR, 0.55; 95% CI, 0.36 to 0.83), while rivaroxaban was associated with a decreased risk of intracranial bleeding (adjusted HR, 0.54; 95% CI, 0.35 to 0.82). As in patients with atrial fibrillation, an increased risk of all-cause mortality was seen in patients taking rivaroxaban (adjusted HR, 1.51; 95% CI, 1.38 to 1.66) and in those on lower doses of apixaban (adjusted HR, 1.34; 95% CI, 1.13 to 1.58).

Overall, apixaban had the lowest numbers needed to treat for six months to avoid one extra major bleed (182 patients with atrial fibrillation and 138 without) compared to warfarin. Rivaroxaban had the lowest numbers needed to harm to observe one extra death over six months (202 patients with atrial fibrillation and 61 without).

The study authors noted limitations to their analysis, such as its observational design and a lack of information on patients' medication adherence. They added that there is also the possibility of some residual confounding and that increases in all-cause mortality may reflect surveillance bias due to the closer monitoring of patients on warfarin.

The study “provides reassurance about the safety of DOACs as an alternative to warfarin across all new incident users,” the authors wrote, although they highlighted one concerning finding. “Rivaroxaban and low dose apixaban were, however, associated with an increased risk of all cause mortality when compared with warfarin.”