Anticoagulants and antiplatelet agents for preventing central venous haemodialysis catheter malfunction in patients with end‐stage kidney disease

Ying Wang; Jessica N Ivany; Vlado Perkovic; Martin P Gallagher; Mark Woodward; Meg J Jardine

doi:10.1002/14651858.CD009631.pub2

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Figure 1

Study flow diagram.

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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Figure 4

Catheter malfunction

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Figure 5

Catheter malfunction (subgroup analysis)

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Figure 6

Catheter‐related bacteraemia

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Figure 7

Catheter‐related bacteraemia (subgroup analysis)

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Figure 8

Exit site infection

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Figure 9

Exit site infection (subgroup analysis)

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Figure 10

Requirement for thrombolytic agents

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Figure 11

Requirement for thrombolytic agents (subgroup analysis)

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Analysis 1.1

Comparison 1 Secondary outcomes, Outcome 1 All‐cause mortality.

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Analysis 1.2

Comparison 1 Secondary outcomes, Outcome 2 Subgroup analysis of all‐cause mortality in alternative anticoagulant locking solutions.

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Analysis 1.3

Comparison 1 Secondary outcomes, Outcome 3 Total bleeding events.

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Analysis 1.4

Comparison 1 Secondary outcomes, Outcome 4 Subgroup analysis of total bleeding events in alternative anticoagulant locking solutions.

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Analysis 1.5

Comparison 1 Secondary outcomes, Outcome 5 Incidence of major bleeding.

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Analysis 1.6

Comparison 1 Secondary outcomes, Outcome 6 Incidence of minor bleeding.

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Table 1. Catheter malfunction events reported by study authors

Study Definition of malfunction	Overall malfunction	Sub‐classification of catheter malfunction events
Study Definition of malfunction	Overall malfunction	Loss due to malfunction	Catheter duration	Interventions to maintain catheter function	Venous occlusion
Alternative anticoagulant locking solutions
Campos 2011 BFR < 200 mL/min for non‐tunnelled and 250 mL/min for tunnelled	Int: 20/92 Cont: 14/95	Int: 20/92 Cont: 14/95	Not reported	Not reported	Not reported
CHARTS Study 2008 BFR < 250 mL/min	Int: 13/32 Cont: 12/39	Int: 25% Cont: 17.2%	Int: 55 days Cont: 90 days	Not reported	Not reported
Dogra 2002 BFR < 200 mL/min	Int: 13/42 Cont: 16/37	Not reported	Not reported	Not reported	Not reported
Filiopoulos 2011 BFR < 250 mL/min	Int: 9/59 Cont: 11/60	Not reported	Not reported	Not reported	Not reported
HEALTHY‐CATH Study 2009 Catheter removal due to flow difficulties	Not reported	Not reported	Not reported	Not reported	Not reported
Hendrickx 2001 BFR < 200 mL/min	Int: 5/10 Cont: 5/9	Not reported	Not reported	Not reported	Int: 105 non‐occlusive clots Cont: 44 non‐occlusive clots
Pervez 2002 BFR < 250 mL/min	Int: 4/14 Cont: 6/19	Not reported	Not reported	Not reported	Not reported
PreCLOT Study 2006 BFR < 200 mL/min	Int: 18/110 Cont: 36/115	Not reported	Not reported	Int: 0/110 Cont: 1/115	Not reported
Solomon 2010 Catheter loss due to occlusion	Int: 8/53 Cont: 3/54	Int: 8/53 Cont: 3/54	Not reported	Not reported	Int: 8/53 Cont: 3/54
Systematic anticoagulants
Abdul‐Rahman 2007 Catheter thrombosis	Int: 4/20 Cont: 9/19	Not reported	Int: 75% survival at 12 months Cont: 36.8% survival at 12 months	Not reported	Int: 4/20 Cont: 9/19
Coli 2006 BFR < 300 mL/min	Int: 10/81 Cont: 33/63	Not reported	Not reported	Not reported	Not reported
Mokrzycki 2001 BFR < 300 mL/min	Int: 8/41 Cont: 8/44	Int: 8/41 Cont: 8/44	Not reported	Not reported	Nor reported
Traynor 2001 BFR < 250 mL/min	Int: 1/10 Cont: 1/8	Not reported	Int: 188 days Cont: 356 days	Not reported	Not reported
Wilkieson 2011 BFR < 150 mL/min	Int: 8/41 Cont: 8/44	Not reported	Not reported	Not reported	Not reported
No or low dose heparin locking solution
Hryszko 2013 Catheter thrombosis	Int: 0/37 Cont: 0/38	Not reported	Not reported	Not reported	Int: 0/37 Cont: 0/38
Kaneko 2004 Catheter thrombosis or BFR < 140 mL/min	Int: 1/26 Cont: 1/22	Not reported	Not reported	Not reported	Int: 1/26 Cont: 1/22
BFR ‐ blood flow rate; Cont ‐ control; Int ‐ intervention

Table 1. Catheter malfunction events reported by study authors

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Table 2. Warfarin dosage and target INR in systemic anticoagulant studies

Study	Number	Intervention arm	Control arm	Background care
Abdul‐Rahman 2007	58	Variable dose warfarin Target INR 1.5 to 2	Placebo	Tinzaparin 40 to 50 IU/kg
Coli 2006	144	Variable dose warfarin Target INR 1.8 to 2.5	Warfarin after catheter malfunction	Ticlopidine 250 mg/d
Mokrzycki 2001	85	Fixed dose warfarin 1 mg/d	Placebo	Heparin 5000 U/mL
Traynor 2001	18	Fixed dose warfarin 1 mg/d	Placebo	Not reported
Wilkieson 2011	174	Variable dose warfarin Target INR 1.5 to 1.9	Placebo	Heparin 1000 to 10,000 U/mL
INR ‐ international normalised ratio

Table 2. Warfarin dosage and target INR in systemic anticoagulant studies

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Comparison 1. Secondary outcomes

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐cause mortality Show forest plot	11	1828	Risk Ratio (M‐H, Random, 95% CI)	0.84 [0.56, 1.27]

1.1 Alternative anticoagulant locking solutions	8	1425	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.54, 1.43]
1.2 Warfarin	3	403	Risk Ratio (M‐H, Random, 95% CI)	0.78 [0.37, 1.65]
2 Subgroup analysis of all‐cause mortality in alternative anticoagulant locking solutions Show forest plot	8	1425	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.54, 1.43]

2.1 Citrate	6	1151	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.52, 1.51]
2.2 rt‐PA	1	225	Risk Ratio (M‐H, Random, 95% CI)	0.63 [0.15, 2.56]
2.3 Ethanol	1	49	Risk Ratio (M‐H, Random, 95% CI)	2.88 [0.12, 67.53]
3 Total bleeding events Show forest plot	7	849	Risk Ratio (M‐H, Random, 95% CI)	0.87 [0.61, 1.25]

3.1 Alternative anticoagulant locking solutions	3	335	Risk Ratio (M‐H, Random, 95% CI)	0.69 [0.47, 1.01]
3.2 Systemic agents	3	439	Risk Ratio (M‐H, Random, 95% CI)	1.30 [0.93, 1.83]
3.3 Low/no dose heparin	1	75	Risk Ratio (M‐H, Random, 95% CI)	0.45 [0.21, 0.96]
4 Subgroup analysis of total bleeding events in alternative anticoagulant locking solutions Show forest plot	7	1074	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.65, 1.19]

4.1 Citrates	2	286	Risk Ratio (M‐H, Random, 95% CI)	0.70 [0.47, 1.02]
4.2 Ethanol	1	49	Risk Ratio (M‐H, Random, 95% CI)	0.32 [0.01, 7.50]
4.3 Warfarin	2	259	Risk Ratio (M‐H, Random, 95% CI)	1.43 [0.86, 2.39]
4.4 Aspirin	1	180	Risk Ratio (M‐H, Random, 95% CI)	1.21 [0.77, 1.90]
4.5 rt‐PA	1	225	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.43, 1.68]
4.6 Low/no dose heparin	1	75	Risk Ratio (M‐H, Random, 95% CI)	0.45 [0.21, 0.96]
5 Incidence of major bleeding Show forest plot	2	286	Risk Ratio (M‐H, Random, 95% CI)	0.58 [0.32, 1.04]

6 Incidence of minor bleeding Show forest plot	2	286	Risk Ratio (M‐H, Random, 95% CI)	0.81 [0.44, 1.50]

Comparison 1. Secondary outcomes

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