Efficacy and Safety of DOACs versus Vitamin K Antagonists in Patients with Atrial Fibrillation and Chronic Kidney Disease undergoing Hemodialysis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with Trial Sequential Analysis.

Background: Atrial fibrillation (AF) is a relatively prevalent arrhythmia in patients with kidney failure requiring dialysis, who face a high risk of stroke and bleeding, and anticoagulation is a challenging decision. Although direct oral anticoagulants (DOACs) may offer advantages over warfarin K antagonists (VKAs), their use in this patient profile remains unclear.

Objective: We conducted a systematic review and meta-analysis to compare DOACs and VKAs in patients with AF undergoing dialysis.

Methods: PubMed, Embase, and Cochrane Central databases were analyzed. The outcomes analyzed were total stroke (a composite of ischemic and hemorrhagic stroke), ischemic stroke, all-cause death, cardiovascular death, myocardial infarction, major bleeding, clinically relevant non-major bleeding and gastrointestinal bleeding. Risk ratios (RRs) with 95% confidence intervals were calculated using a random effects model. R software (version 4.3.2) was used for statistical analyses. Heterogeneity was assessed with I2 statistics.

Results: The final analysis included 486 patients from 4 RCT studies. The median follow-up ranged from 5.8 to 18 months. Although a reduction in total stroke was observed in the group receiving DOACs (RR 0.40; 95% CI 0.17 - 0.92; p=0.031; I2 =0%), no significant difference was found between the groups for ischemic stroke (RR 0.42; 95% CI 0.17 - 1.04; p=0.062; I2 =0%). Additionally, a statistically significant reduction in major bleeding was noted in the DOAC group (RR 0.64; 95% CI 0.41 - 0.98; p=0.044; I2 = 0%). However, no significant differences were observed between the groups for all-cause death (RR 0.88; 95% CI 0.57 - 1.35; p=0.567; I2 =47%), cardiovascular death (RR 1.13; 95% CI 0.60 - 2.10; p=0.700; I2 =0%), or clinically relevant non-major bleeding (RR 1.11; 95% CI 0.67 - 1.84; p=0.669; I2 = 0%).

Conclusions: In this meta-analysis, DOACs were associated with a lower risk of total stroke and major bleeding. However, DOACs and VKA groups exhibited similar rates of ischemic stroke, all-cause and cardiovascular death, clinically relevant non-major bleeding and gastrointestinal bleeding.