Real-world data suggest that apixaban poses a lower risk of bleeding than warfarin, but patients who receive lower doses of apixaban have an increased risk of all-cause mortality.
Compared to warfarin, apixaban was associated with a decreased risk of major bleeding, intracranial bleeding, and gastrointestinal bleeding in certain patients.
Dabigatran and rivaroxaban were associated with a decreased risk of intracranial bleeding for certain patients, compared to warfarin.
However, patients who received rivaroxaban or lower doses of apixaban had an increased risk of all-cause mortality, compared to patients who received warfarin.
Yana Vinogradova, PhD, of University of Nottingham in the UK, and her colleagues reported these results in The BMJ.
The researchers set out to investigate the risks and benefits associated with apixaban, dabigatran, and rivaroxaban compared with warfarin in patients with and without atrial fibrillation (AF).
Using data from 2 large UK primary care databases, the researchers identified 196,061 patients who started or restarted anticoagulants (after more than a 12-month gap) between 2011 and 2016.
There were 132,231 patients taking warfarin, 7744 on dabigatran, 37,863 on rivaroxaban, and 18,223 on apixaban.
Slightly more than half of patients (53%, n=103,270) were diagnosed with AF, and 47% (n=92,791) were prescribed anticoagulants for other conditions.
When compared to warfarin in patients with AF, apixaban was associated with a decreased risk of:
- Major bleeding—adjusted hazard ratio [aHR]=0.66
- Intracranial bleeding—aHR=0.40.
In patients without AF, apixaban was associated with a decreased risk of:
- Major bleeding—aHR=0.60
- Any gastrointestinal bleeding—aHR=0.55
- Upper gastrointestinal bleeding—aHR=0.55.
In patients with AF, dabigatran was associated with a decreased risk of intracranial bleeding—aHR=0.45—compared to warfarin.
In patients without AF, rivaroxaban was associated with a decreased risk of intracranial bleeding—aHR=0.54—compared to warfarin.
Compared to patients taking warfarin, there was an increased risk of all-cause mortality for patients:
- With AF taking rivaroxaban—aHR=1.19
- Without AF taking rivaroxaban— aHR=1.51
- With AF taking lower doses of apixaban—aHR=1.27
- Without AF taking lower doses of apixaban—aHR=1.34.
The researchers said the increased risk of all-cause mortality in these patients may reflect the fact that patients taking warfarin are monitored more closely, or it may be related to underlying conditions.
The team did point out that this is an observational study, so no firm conclusions can be drawn about cause and effect. They also outlined some limitations, such as possible misclassification due to patients not taking their medication.
Nevertheless, the researchers concluded that “the risk of major bleeding is lower in apixaban users, regardless of the reason for prescribing, appearing to show apixaban to be the safest drug.”