Apixaban was the clear winner in a large observational study looking at the risk of major bleeding and death with the use of the most commonly prescribed anticoagulants.
The study, which breaks new ground in terms of its scope and design, looked at around 200,000 new users of warfarin, dabigatran, rivaroxaban and apixaban in the UK primary care setting, tracking them over a five-year period. Overall, apixaban was found to be the safest direct oral anticoagulant (DOAC) compared with warfarin for patients with and without atrial fibrillation. Patients on a standard dose of apixaban had a 34% reduced risk of major bleeding and a 60% lower risk of intracranial bleeding over the study period, compared with warfarin. Apixaban users also had reduced rates of gastrointestinal bleeding.
The safety benefits of other DOACs compared with warfarin was less clear cut. There was a reduced risk of intracranial bleeds with rivaroxaban, but only in patients without atrial fibrillation. And in patients with atrial fibrillation, dabigatran lowered the risk of intracranial bleed, compared with warfarin.
Rivaroxaban was associated with higher all-cause mortality across the board, in patients both with and without atrial fibrillation, as was apixaban in low doses, compared with warfarin. But the authors say the higher mortality with these DOAC regimens could be due to closer monitoring of patients on warfarin, or due to prescribing choices related to underlying comorbidities.
The stronger safety profile of apixaban in this study is in line with a recent meta-analysis, which also showed apixaban to be the safest of the DOACs and a better performer than warfarin. But the authors of the present study say that meta-analysis mostly involved indirect rather than head-to-head comparisons. Direct comparison studies are few and far between, because regulatory authorities generally only require studies showing non-inferiority to placebo or standard treatment.
They add that their study is the first to look at a large subset of patients taking anticoagulants for reasons other than atrial fibrillation, such as after deep vein thrombosis, knee or hip replacement or stroke. This accounts for about half of users of anticoagulants.
Overall, they say their study paints a reassuring picture for patients taking DOACs as an alternative to warfarin, particularly for those who have been prescribed apixaban.
You can access the full study here.