METHODS AND FINDINGS: We performed a literature search (up to January 2014), clinical trials registers, conference proceedings, and websites of regulatory agencies. We selected non-inferiority randomised controlled phase III trials of
dabigatran,
rivaroxaban,
apixaban and
edoxaban compared with adjusted-dose
warfarin in non-valvular AF. Compared to imputed placebo, all NOACs reduced the risk of
stroke (
ORs between 0.24 and 0.42, all p<0.001) and all-cause mortality (
ORs between 0.55 and 0.59, all p<0.05).
Edoxaban 30 mg and 60 mg preserved 87% and 112%, respectively, of the protective effect of
warfarin on
stroke, and 133% and 121%, respectively, of the protective effect of
warfarin on all-cause mortality. The risk of primary outcome (
stroke/systemic
embolism), all
strokes and
ischemic strokes was significantly higher with
edoxaban 30 mg than
dabigatran 150 mg and
apixaban. There were no significant differences between
edoxaban 60 mg and other NOACs for all efficacy outcomes except
stroke, which was higher with
edoxaban 60 mg than
dabigatran 150 mg. The risk of major bleedings was lower with
edoxaban 30 mg than any other
NOAC, odds ratios (
ORs) ranging between 0.45 and 0.67 (all p<0.001).
CONCLUSIONS: This study suggests that all NOACs preserve a substantial or even larger proportion of the protective
warfarin effect on
stroke and all-cause mortality.
Edoxaban 30 mg is associated with a definitely lower risk of major bleedings than other NOACs. This is counterbalanced by a lower efficacy in the prevention of
thromboembolism, although with a final benefit on all-cause mortality.