Meta-Analysis of Renal Function on the Safety and Efficacy of Novel Oral Anticoagulants for Atrial Fibrillation

Abstract

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.