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; I² = 66%), but not for stroke/systematic embolism (HR = 0.90; 95% CI, 0.72–1.14; P = 0.40; I² = 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; I² = 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; I² = 61%) and significantly lower risk of safety outcomes (HR = 0.66; 95% CI, 0.58–0.76; P < 0.0001; I² = 0%), particularly major bleeding (HR = 0.63; 95% CI, 0.53–0.76; P < 0.0001; I² = 0%) and intracranial hemorrhage (HR = 0.43; 95% CI, 0.30–0.62; P < 0.0001; I² = 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.