Efficacy and Safety of Direct Oral Anticoagulants for Patients With Atrial Fibrillation With Glomerular Hyperfiltration: A Systematic Review and Meta-Analysis

Purpose The purpose of this study was to identify possible therapeutic benefits of direct oral anticoagulants (DOACs) compared with warfarin in subjects with supranormal renal function. Methods PubMed and Embase were systematically searched until September 25, 2022. Articles that met the prespecified selection criteria were included. The fixed-effects model was chosen if there is no significant heterogeneity. Subgroup analyses were conducted to find the sources of heterogeneity. Variables that might expand heterogeneity were selected as follows: (1) type of DOAC, (2) dose of DOAC, (3) equation for glomerular filtration rate estimation, and (4) types of original research. Findings A total of 7 studies involving 87,514 patients were included. In patients with creatinine clearance (CrCl) >80 mL/min, DOACs were associated with a significant reduction in the overall effectiveness outcomes compared with warfarin (hazard ratio [HR] = 0.75; 95% CI, 0.66–0.86; P < 0.0001; I 2 = 66%), but not for stroke/systematic embolism (HR = 0.90; 95% CI, 0.72–1.14; P = 0.40; I 2 = 17%). Similarly, DOACs showed a decreased risk of safety outcomes compared with warfarin (HR = 0.68; 95% CI, 0.63–0.74; P < 0.0001; I 2 = 45%). In patients with CrCl >95 mL/min, DOACs were associated with a borderline lower risk of effectiveness outcomes (HR = 0.83; 95% CI, 0.68–1.01; P = 0.07; I 2 = 61%) and significantly lower risk of safety outcomes (HR = 0.66; 95% CI, 0.58–0.76; P < 0.0001; I 2 = 0%), particularly major bleeding (HR = 0.63; 95% CI, 0.53–0.76; P < 0.0001; I 2 = 0%) and intracranial hemorrhage (HR = 0.43; 95% CI, 0.30–0.62; P < 0.0001; I 2 = 0%). Implications In patients with atrial fibrillation and CrCl >80 mL/min, DOACs have greater clinical benefits than warfarin. For those with atrial fibrillation and CrCl >95 mL/min, significantly better safety outcomes were observed for DOACs.