. 2020 Sep 29;22(3):306–316. doi: 10.5853/jos.2020.01886

Table 2.

Pharmacologic agents and outcomes in ESRD patients with AF

Study year		Author	Study design	Study participants	Outcome	Stroke/thromboembolism	Bleeding
Antiplatelet agent: aspirin
	1997–2008	Olesen et al. [5]	Retrospective observational (Cox-regression analysis)	All patients discharged from the hospital with a diagnosis of non-valvular AF (n=901)	Primary: hospitalization or death from stroke or systemic thromboembolism, bleeding	HR, 0.88; 95% CI, 0.59–1.32; P=0.54	HR, 1.63; 95% CI, 1.18–2.26; P=0.003
	1997–2008	Olesen et al. [5]	Retrospective observational (Cox-regression analysis)		Secondary: risk of stroke or systemic thromboembolism (excluding TIA)	HR, 0.88; 95% CI, 0.59–1.32; P=0.54	HR, 1.63; 95% CI, 1.18–2.26; P=0.003
	1997–2011	Bonde et al. [44]	Retrospective observational	All patients discharged from hospital with diagnosis of non-valvular AF and RRT (n=1,728)	Hospitalization/death from stroke/thromboembolism, a composite of fatal stroke/fatal bleeding	HR, 1.82; 95% CI, 1.55–2.14	HR for all stroke or all bleeding 1.06; 95% CI, 0.83–1.36^*
	1998–2006	Chen et al. [43]	Retrospective observational	ESRD patients on dialysis after first‐time ischemic stroke (n=1,936)	Primary: death and readmission to hospital for stroke	HR for primary outcomes in patients treated with aspirin, 0.67; P<0.001	HR, 0.89; P=0.291
	1998–2006	Chen et al. [43]	Retrospective observational		Secondary: death, stroke or bleeding	HR for readmission for stroke, 0.72; P=0.002	HR, 0.89; P=0.291
Vitamin K antagonist: warfarin
	1997–2008	Olesen et al. [5]	Retrospective observational (Cox-regression analysis)	All patients discharged from the hospital with a diagnosis of non-valvular AF (n=901)	Primary-hospitalization or death from stroke or systemic thromboembolism, bleeding	With warfarin use: HR, 0.44; 95% CI, 0.26–0.74; P=0.002	HR, 1.27; 95% CI, 0.911–1.77; P=0.15
	1997–2008	Olesen et al. [5]	Retrospective observational (Cox-regression analysis)		Secondary: risk of stroke or systemic thromboembolism (excluding TIA)	With warfarin use: HR, 0.44; 95% CI, 0.26–0.74; P=0.002	HR, 1.27; 95% CI, 0.911–1.77; P=0.15
	1997–2011	Bonde et al. [44]	Retrospective observational	All patients discharged from hospital with diagnosis of non-valvular AF and RRT (n=1,728)	Hospitalization/death from stroke/thromboembolism, a composite of fatal stroke/fatal bleeding	Rate per 100 person-years with use of warfarin, 4.8; 95% CI, 3.2–6.4; as compared to no warfarin, 7.3; 95% CI, 6.2–8.5	HR for all stroke/bleeding, 1.06; 95% CI, 0.83–1.36
	1998–2007	Shah et al. [61]	Retrospective cohort	Patients aged ≥65 years admitted to a hospital with a diagnosis of AF (dialysis patients n=1,626)	First hospital admission or emergency department visit for stroke or bleeding	Stroke: HR, 1.14; 95% CI, 0.78–1.67	Bleeding: HR, 1.44; 95% CI, 1.13–1.85
	2002–2015	Abuhasira et al. [4]	Retrospective cohort	All patients who initiated dialysis during the study period and developed AF (n=304)	CVA and major bleeding event	Risk of CVA with use of warfarin as compared to no warfarin (24.2% vs. 12.9%, P=0.026)	Risk with use of warfarin as compared to no warfarin (16.7% vs. 9.2%, P=0.09)
	2006–2013	Waddy et al. [10]	Retrospective observational cohort	ESRD patients who initiated HD and subsequently diagnosed with AF (n=56,587)	Primary outcome: all-cause stroke	Ischemic stroke: aHR, 0.79; 95% CI, 0.66–0.95	GI bleeding: aHR, 1.12; 95% CI, 0.94–1.36
	2006–2013	Waddy et al. [10]	Retrospective observational cohort		Secondary outcomes: death, ischemic stroke, hemorrhagic stroke, GI bleeding	Ischemic stroke: aHR, 0.79; 95% CI, 0.66–0.95	Hemorrhagic stroke: aHR, 1.22; 95% CI, 1.03–1.46
	2006–2015	Kai et al. [62]	Propensity scorematched cohort	ESRD patients with AF (n=888)	Stroke, bleeding, and death	Ischemic stroke: HR, 0.68; 95% CI, 0.52–0.91	GI bleeding: HR, 0.97; 95% CI, 0.77–1.2
	2006–2015	Kai et al. [62]	Propensity scorematched cohort	ESRD patients with AF (n=888)	Stroke, bleeding, and death	Ischemic stroke: HR, 0.68; 95% CI, 0.52–0.91	Hemorrhagic stroke: HR, 1.2; 95% CI, 0.6–2.2
	2007–2011	Shen et al. [63]	Retrospective observational cohort	ESRD patients on HD with new diagnosis of AF and no prior use of warfarin (n=12,284)	Death, ischemic stroke, hemorrhagic stroke, and severe GI bleeding	Ischemic stroke: HR, 0.68; 95% CI, 0.47–0.99	GI bleeding: HR, 1.00; 95% CI, 0.69–1.44
	2007–2011	Shen et al. [63]	Retrospective observational cohort			Ischemic stroke: HR, 0.68; 95% CI, 0.47–0.99	Hemorrhagic stroke: HR, 0.82; 95% CI, 0.37–1.81
	2009–2013	Yoon et al. [64]	Propensity matched cohort	Patients with ESRD and AF (n=5,548)	Ischemic stroke, hemorrhagic stroke, and GI bleeding	Ischemic stroke: HR, 0.95; 95% CI, 0.78–1.15; P=0.569	GI bleeding with the warfarin use (7.5%) and no warfarin use (6.6%), P=0.208
	2009–2013	Yoon et al. [64]	Propensity matched cohort	Patients with ESRD and AF (n=5,548)	Ischemic stroke, hemorrhagic stroke, and GI bleeding	Ischemic stroke: HR, 0.95; 95% CI, 0.78–1.15; P=0.569	Hemorrhagic stroke: HR, 1.56, 95% CI, 1.10–2.22; P=0.013
Direct oral anticoagulant: apixaban
	2010–2015	Siontis et al. [57]	Retrospective cohort	Patients with AF and ESRD undergoing dialysis who initiated treatment with an oral anticoagulant (n=25,523)	Stroke or systemic embolism, major bleeding, GI bleeding, intracranial bleeding, and death	Stroke/systemic embolism for apixaban vs. warfarin: HR, 0.88; 95% CI, 0.69–1.12; P=0.29	GI bleeding for apixaban vs. warfarin: HR, 0.86; 95% CI, 0.72–1.02; P=0.09
	2010–2015	Siontis et al. [57]	Retrospective cohort				Intracranial bleed for apixaban vs. warfarin: HR, 0.79; 95% CI 0.49–1.26; P=0.32
	2017	Chokesuwattanaskul et al. [58]	Meta-analysis	Studies that reported bleeding complications or thromboembolic events in the use of apixaban in patients with CKD stage 4–5 or ESRD on dialysis (5 studies, 43,850 patients)	Thromboembolic event, major bleeding	Pooled OR, 0.56; 95% CI, 0.23–1.39	Pooled OR, 0.42; 95% CI, 0.28–0.61
	2019	Kuno et al. [59]	Meta-analysis	Studies that investigated the efficacy and safety of different OAC strategies in patients with AF on longterm dialysis	Ischemic stroke/systemic thromboembolism, major bleeding, and all-cause mortality	As compared to no-anticoagulation, Apixaban 2.5 mg: HR, 1.00; 95% CI, 0.52–1.93 Apixaban 5 mg: HR, 0.59; 95% CI, 0.30–1.17	Risk of bleeding with warfarin as compared to Apixaban 2.5 mg: HR, 1.40; 95% CI, 1.07–1.82 Apixaban 5 mg: HR 1.41; 95% CI, 1.07–1.88
	2020	Mavrakanas et al. [65]	Propensity cohort	Patients on maintenance dialysis with incident, nonvalvular AF treated with apixaban (n=521)	Primary outcome: hospitalization for new CVA, TIA, or systemic thromboembolism	Ischemic stroke for apixaban as compared to no treatment: HR, 0.85; 95% CI, 0.36–1.98; P=0.71	Major bleeding for apixaban as compared to no treatment: HR, 2.76; 95% CI, 1.38–5.52; P=0.004
	2020	Mavrakanas et al. [65]	Propensity cohort		Secondary outcome: fatal or intracranial bleeding		Hemorrhagic stroke for apixaban as compared to no treatment: HR, 1.89; 95% CI, 0.65–5.49; P=0.24

ESRD, end-stage renal disease; AF, atrial fibrillation; TIA, transient ischemic attack; HR, hazard ratio; CI, confidence interval; RRT, renal replacement therapy; CVA, cerebrovascular accident; HD, hemodialysis; GI, gastrointestinal; aHR, adjusted hazard ratio; CKD, chronic kidney disease; OR, odds ratio; OAC, oral anticoagulants.

High risk (CHA₂DS₂-VASc score ≥2).