Novel oral
anticoagulants (NOACs) are safe and effective for the prevention of
stroke or systemic
embolism (S/SE) in
atrial fibrillation. The efficacy and safety of NOACs compared with
warfarin has not been systematically assessed in subjects with mild or moderate renal dysfunction. We performed a meta-analysis of the randomized clinical trials that compared efficacy and safety (major
bleeding) outcomes of NOACs compared to
warfarin for the treatment of nonvalvular
atrial fibrillation and had available data on renal function. We estimated the pooled relative risk (RR) of S/SE and major
bleeding in relation to renal function (assessed by baseline estimated glomerular filtration rate divided in 3 groups: normal [estimated glomerular filtration rate >80 ml/min], mildly impaired [50 to 80 ml/min], and moderate impairment [<50 ml/min]). We included 4 randomized clinical trials enrolling a total of 58,338 subjects. The RRs of S/SE and major
bleeding were higher in subjects with renal impairment compared to normal renal function, independent of type of
anticoagulant therapy. In subjects with normal renal function, no difference in the risk of S/SE was observed, whereas the risk of major
bleeding was slightly lower for subjects taking NOACs (RR 0.87, 95% confidence interval [CI] 0.76 to 0.99). In subjects with mild or moderate renal impairment, NOACs were associated with a reduced risk of S/SE (RR 0.75, 95% CI 0.66 to 0.85 and RR 0.80, 95% CI 0.68 to 0.94, respectively) and major
bleeding (RR 0.87, 95% CI 0.79 to 0.95 and RR 0.80, 95% CI 0.71 to 0.91, respectively) compared to
warfarin. The pooled analysis for major
bleeding demonstrated significant heterogeneity. In conclusion, the use of NOACs was associated with a reduced risk of S/SE and reduced risk of major
bleeding compared to
warfarin in subjects with mild or moderate renal impairment suggesting a favorable risk profile of these agents in patients with renal disease.