OBJECTIVES: A comparative analysis of three major clinical trials with factor Xa 
inhibitor oral anticoagulant (XOAC) drugs versus warfarin in atrial 
fibrillation-Rocket-AF (rivaroxaban), Aristotle (apixaban) and Engage AF Timi 48 
(edoxaban; two different doses and sets of data)-was carried out.
METHODS: Data were extracted from the original reports (study level) and a 
meta-analysis was carried out.
RESULTS: When compared with warfarin, XOAC therapy was associated with a 
decrease in haemorrhagic stroke, with a similar pattern for all regimens and 
meta-analysis showing a risk ratio of 0.488 (95% CI 0.396 to 0.601). Regarding 
total mortality, a favourable pattern was seen for all four regimens and 
meta-analysis showed a risk ratio of 0.892 (95% CI 0.840 to 0.947). Major 
bleeding and gastrointestinal bleeding provided two examples regarding which 
heterogeneity would seem to exist, when XOAC drugs are compared with warfarin. 
In what concerns the incidence of myocardial infarction, the primary end point 
(stroke plus systemic embolism) and ischaemic stroke, the situation is less 
clear. These results are inconsistent with a putative 'group effect' for all the 
seven parameters under study, and for some of them it would probably be best to 
look at each of the individual trial data rather than at the meta-analysis data 
(which seem to lack a clear biological meaning).
CONCLUSIONS: Apixaban, rivaroxaban and edoxaban have shown interesting effects, 
when compared with warfarin in clinical trials, in patients with atrial 
fibrillation, particularly with regard to haemorrhagic stroke and to the 
mortality rate. No other consistent conclusions concerning a putative 'group 
effect' can be reached at the present stage. Concerns regarding adherence to 
therapy, possible drug interactions, cost and current absence of antidotes may 
be taken into consideration when choosing an anticoagulant drug.