Effectiveness and safety of direct oral anticoagulants in patients with atrial fibrillation and chronic kidney disease: a systematic review and meta-analysis of clinical trials

Aim. To analyze published clinical trials to evaluate the safety and effectiveness of direct oral anticoagulants in comparison with warfarin in a population of patients with atrial fibrillation and chronic kidney disease stages C4-C5. Material and methods. The meta-analysis was conducted in accordance with PRISMA guidelines based on a literature search in the PubMed/MEDLINE database for the period from 01 January 2018 to 25 December 2023. Keywords included the MeSH terms "atrial fibrillation" and "dialysis" or "hemodialysis" or "end-stage kidney disease" or "end-stage renal disease" or "advanced renal disease" or "stage 4 or 5 chronic kidney disease" or "stage 5 chronic kidney disease" and "non-vitamin K antagonist oral anticoagulants" or "direct oral anticoagulants" or "novel oral anticoagulant" or "NOAC" or "DOAC" or "dabigatran" or "apixaban" or "rivaroxaban" and "vitamin K antagonist" or "warfarin" and "outcomes". ROBINS-I and RoB2 tools were used to assess the systematic error of the research. Results. When searching the literature based on the chosen strategy, 1,895 publications were selected, some of which were excluded due to inconsistency with the inclusion criteria; as a result, 13 studies that did not have exclusion criteria were included in the analysis. The meta-analysis included 60,109 patients from 13 studies, 9,991 of whom received direct oral anticoagulants and 50,118 received warfarin. The results showed that in patients with stage C4-C5 chronic kidney disease treated with direct oral anticoagulants, ischemic stroke/systemic embolism was 26% less likelyto develop compared with warfarin (HR=0.74, 95% CI 0.57-0 .95, p=0.02). The pooled effect of direct oral anticoagulant treatment demonstrated a lower risk of major bleeding (HR=0.74, 95% CI 0.67-0.82, p<0.001). There was a trend towards a reduction in the risks of both intracranial hemorrhage (HR=0.70, 95% CI 0.49-1.00, p=0.05) and major gastrointestinal bleeding compared with warfarin (HR=0.87, 95% CI 0.76-1.00, p=0.05). When analyzing all-cause mortality, direct oral anticoagulanttherapy was also associated with a 14% reduction (HR=0.86, 95% CI 0.80-0.92, p<0.001). Conclusion. Our meta-analysis shows that in a population of patients with atrial fibrillation and stage C4 and C5 chronic kidney disease, therapy with direct oral anticoagulants compared with warfarin is associated with greater effectiveness and safety in reducing the risks of ischemic stroke/systemic embolism and major bleeding.