title: Anticoagulants and antiplatelet agents for preventing central venous haemodialysis catheter malfunction in patients with end-stage kidney disease.
abstract: BACKGROUND
  Catheter malfunction, including thrombosis, is associated with reduced dialysis adequacy, as well as an increased risk of catheter-related bacteraemia and mortality. The role of anticoagulants in the prevention of catheter malfunction remains uncertain.
  
  
  OBJECTIVE
  This review aimed to compare the prophylactic effect of different anticoagulant agents, preparations, doses and administration on the incidence of central venous haemodialysis catheter-related malfunction and sepsis in patients with end-stage kidney disease (ESKD).
  
  
  METHODS
  We searched the Cochrane Renal Group's Specialised Register to 7 January 2016 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.
  
  
  METHODS
  We included all randomised controlled trials (RCT) assessing anticoagulants compared with conventional care for the prevention of catheter malfunction in adult patients receiving haemodialysis for ESKD.
  
  
  METHODS
  The primary outcome was catheter malfunction defined as a catheter blood flow of 200 mL/min or less, or as defined by study authors. Secondary outcomes were catheter-related bacteraemia, all-cause mortality and bleeding events. Relative risks (RR) with 95% confidence intervals (CI) for individual studies were pooled using random effects models within treatment classes. Analyses were conducted by class, with subgroup analyses performed of individual agents within classes.
  
  
  RESULTS
  We included 27 studies (3003 participants) that were followed up for a median of six months. Study interventions included alternative anticoagulant locking solutions (19 studies, 2216 patients), systemic agents (6 studies, 664 patients) and low or no dose heparin (2 studies, 123 patients). The most common comparison treatment was a locking solution of heparin 5000 IU/mL, used in 17 studies. No significant effect on catheter malfunction was observed for alternative anticoagulant locking solutions (RR 0.96, 95% CI 0.74 to 1.26), systemic agents (RR 0.59, 95% CI 0.28 to 1.23), or low or no dose heparin (RR 0.90, 95% CI 0.10 to 8.31). A significant reduction on incidence of catheter-related bacteraemia was observed for alternative anticoagulant locking solutions (RR 0.46, 95% CI 0.32 to 0.66) but not systemic agents (RR 2.41, 95% CI 0.89 to 6.55), and could not be assessed in reports of low or no dose heparin studies. No significant effect on all-cause mortality was observed for alternative anticoagulant locking solutions (RR 0.88, 95% CI 0.54 to 1.43) or systemic agents (RR 0.78, 95% CI 0.37 to 1.65), and was not reported in studies of low or no dose heparin. Bleeding events were only reported in eight studies, including only 2/5 studies of systemic warfarin, with no clear effect demonstrated (RR 1.43, 95% CI 0.86 to 2.39). For individual agents, recombinant tissue plasminogen (rt-PA) was the only locking solution shown to reduce catheter malfunction (RR 0.58, 95% CI 0.37 to 0.91) based on the results of a single study. No significant on catheter malfunction was observed for other individual classes of alternative anticoagulant locking solutions (citrate: RR 1.14, 95% CI 0.76 to 1.69; antibiotic: RR 1.48, 95% CI 0.79 to 2.77; ethanol: RR 0.88, 95% CI 0.21 to 3.67). On the other hand, all individual classes of alternative anticoagulant locking solutions, except ethanol, reduced catheter-related bacteraemia (citrate: RR 0.49, 95% CI 0.36 to 0.68; antibiotic: RR 0.27, 95% CI 0.11 to 0.70; rt-PA: RR 0.35, 95% CI 0.13 to 0.93; ethanol: RR 0.33, 95% CI 0.03 to 4.05). No significant effect on all-cause mortality was observed for any individual agent within the class of alternative locking solutions. Studies were mainly of low quality and underpowered with an average participant number of 75 and study duration of six months. The interpretation of the study evidence was further limited by the variation in tested interventions and outcome reporting.
  
  
  CONCLUSIONS
  The relative net benefit of anticoagulant therapies for prevention of catheter malfunction remains uncertain. Multiple agents appear to reduce catheter-related bacteraemia although the lack of clear assessment of harms and the limitations of study quality mean these results should be interpreted with caution. Methodological approaches can be used to avoid methods of reporting unduly affecting on the results of meta-analyses incorporating studies employed mixed reporting methods. Further high quality randomised studies, including safety outcomes, are needed.
authors.affiliation: Renal and Metabolic Division, The George Institute for Global Health, The University of Sydney, Level 10, King George V Building, 83-117 Missenden Rd, Camperdown, NSW, Australia, 2050.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Ivany
authors.forename: Vlado
authors.initials: V
authors.lastname: Perkovic
authors.forename: Martin P
authors.initials: MP
authors.lastname: Gallagher
authors.forename: Mark
authors.initials: M
authors.lastname: Woodward
authors.forename: Meg J
authors.initials: MJ
authors.lastname: Jardine
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage*; D016470:Bacteremia / Q000517:prevention & control; D061807:Catheter Obstruction; D055499:Catheter-Related Infections / Q000517:prevention & control; D062905:Central Venous Catheters; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D006435:Renal Dialysis / Q000295:instrumentation*
chemical_list: D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D006493:Heparin