Management of anticoagulation in patients with atrial fibrillation and renal dysfunction: A systematic review

Table 1 Quality assessment for randomized controlled trials (Cochrane risk of bias)

Ref.	Random bias	Blinding bias	Deviations from intended interventions	Missing outcome data	Outcome measurement bias	Selective reporting bias	Overall risk of bias
Connolly et al[1]	Low	Low	Low	Low	Low	Low	Low
Granger et al[2]	Low	Low	Low	Low	Low	Low	Low
Patel et al[3]	Low	Moderate	Low	Moderate	Low	Low	Moderate
Giugliano et al[33]	Low	Moderate	Low	Low	Low	Low	Low
Harel et al[10]	High	High	Moderate	Moderate	Moderate	Low	High

Table 2 Quality assessment for observational studies (Newcastle-Ottawa Scale)

Ref.	Selection (4)	Comparability (2)	Outcome (3)	Total score (9)
Chan et al[14]	4	1	2	7
Winkelmayer et al[15]	4	2	3	9
Siontis et al[9]	4	2	3	9
Weitz et al[20]	4	2	3	9
Lai et al16]	4	2	3	9
Pisters et al[11]	4	2	3	9
Van Bulck et al[19]	4	2	3	9
Yao et al[7]	4	1	2	8
Matusik et al[6]	4	2	3	9
Liabeuf et al[18]	4	2	3	9
Akbar et al[17]	4	2	3	9

Table 3 Elaborated summary of 16 studies on anticoagulation in atrial fibrillation and chronic kidney disease

Ref.	Study design	Sample size	Follow-up duration (year)	Population	Intervention	Key outcomes
Chan et al[14]	Retrospective Cohort Study	2740	1.6	End-stage renal disease patients with atrial fibrillation	Warfarin (vs nonuse), clopidogrel (vs noanuse), aspirin (vs nonuse)	End-stage renal disease patients with coexistent atrial fibrillation are at a significantly higher risk of suffering from a stroke when using warfarin
Connolly et al[1]	Randomized Controlled Noninferiority Trial	18113	2.0	Atrial fibrillation patients, moderate renal impairment	Dabigatran vs Warfarin	Demonstrated that dabigatran significantly reduced the risk of stroke compared to warfarin in atrial fibrillation patients with moderate renal impairment, though increased bleeding risk was observed
Granger et al[2]	Randomized Controlled Trial, double-blind	18201	1.8	Atrial fibrillation patients, all chronic kidney disease stages	Apixaban vs Warfarin	Showed that apixaban reduced bleeding risk and mortality compared to warfarin, including in chronic kidney disease subgroups, making it a safer alternative for atrial fibrillation patients with renal dysfunction
Patel et al[3]	Randomized Controlled Trial, double-blind	14264	1.9	Atrial fibrillation patients, moderate renal impairment	Rivaroxaban vs Warfarin	Highlighted rivaroxaban's comparable efficacy to warfarin in preventing stroke in atrial fibrillation patients, with bleeding risks affected by renal impairment and dosing strategies
Giugliano et al[33]	Randomized Controlled Trial, double-blind, double-dummy trial	21105	2.8	Atrial fibrillation patients, moderate to severe chronic kidney disease	Edoxaban vs Warfarin	Reported edoxaban as an effective alternative to warfarin in atrial fibrillation patients with moderate to severe chronic kidney disease, but with a need for careful dose adjustment to minimize bleeding risks
Harel et al[10]	Randomized Controlled Trial, open-label, pilot study	151	0.5	Dialysis patients with Atrial fibrillation	Direct oral anticoagulants vs Vitamin K antagonists	A pilot randomized controlled trial exploring direct oral anticoagulants use in dialysis patients, indicating potential efficacy but underscoring the importance of individualized therapy in this complex subgroup
Siontis et al[9]	Retrospective Cohort Study	25523	0.4	End-stage renal disease patients with atrial fibrillation	Apixaban use	Revealed lower bleeding rates with apixaban use compared to warfarin in end-stage renal disease patients, supporting its safety and effectiveness in advanced chronic kidney disease populations
Weitz et al[20]	Randomized Controlled Trial, single blind	1242	0.1	Venous thromboembolism prevention population	Milvexian for thromboembolism prevention	Focused on milvexian for venous thromboembolism prevention but emphasized the potential applicability of novel anticoagulants in chronic kidney disease-related atrial fibrillation management
Pisters et al[11]	Retrospective Cohort Study	3978	1.0	Atrial fibrillation patients with bleeding risk	HAS-BLED score	Developed the HAS-BLED score as a bleeding risk prediction tool, with potential for modification to better suit chronic kidney disease-specific bleeding risk assessment
Van Bulck et al[19]	Retrospective Mortality Study	390	NA	Congenital heart disease patients	Patterns of care in terminal illness	Explored causes of death and care patterns in congenital heart disease patients, indirectly addressing the challenges of anticoagulation in comorbid conditions like chronic kidney disease
Yao et al[7]	Retrospective Cohort Study	14865	0.3	Atrial fibrillation patients with renal dysfunction	Direct oral anticoagulants dosing strategies	Examined direct oral anticoagulants dosing adherence in atrial fibrillation patients with renal dysfunction, identifying inappropriate dosing as a significant contributor to adverse outcomes
Lai et al[16]	Retrospective Cohort Study	399	2.5	Patients with chronic kidney disease and nonvalvular atrial fibrillation	Warfarin (vs nonuse)	Warfarin use was not associated with increase in the incidence of major bleeding events in the chronic kidney disease patients. There was no statistically significant difference between bleeding episodes in both groups
Matusik et al[6]	Prospective Cohort Study	180	2.0	Atrial fibrillation and stage 4 chronic kidney disease patients	Biomarkers and thromboembolism risk	Assessed biomarkers like cystatin C in predicting thromboembolism and bleeding risks in stage 4 chronic kidney disease, advocating for precision medicine in anticoagulation therapy
Liabeuf et al[18]	Post-hoc Analysis	6559	3.0	Moderate-to-advanced chronc kidney disease with Atrial fibrillation	Direct oral anticoagulants prescriptions	Explored direct oral anticoagulants prescription patterns in moderate-to-advanced chronic kidney disease, identifying underuse due to clinician concerns about bleeding risks and patient monitoring challenges
Winkelmayer et al[15]	Retrospective Cohort Study	2313	1.8	End-stage renal disease patients with atrial fibrillation	Warfarin (vs nonuse)	Warfarin use in the end-stage renal disease patients who had a history of atrial fibrillation was associated significantly with hemorrhagic stroke; however, it lowered the risk of ischemic stroke
Akbar et al[17]	Retrospective Cohort Study	88	0.9	End-stage renal disease patients with atrial fibrillation	Warfarin (vs nonuse)	Use of warfarin in hemodialysis patients with atrial fibrillation was not associated with lower risk of death, stroke incidence, and hemorrhagic stroke. However, the risk of myocardial infarction was reduced significantly