title: Anticoagulant therapies for the prevention of intravascular catheters malfunction in patients undergoing haemodialysis: systematic review and meta-analysis of randomized, controlled trials.
abstract: BACKGROUND
  Catheter malfunction (CM), including thrombosis, is associated with reduced dialysis adequacy, as well as an increased risk of catheter-related bacteraemia (CRB) and mortality. The role of alternative anticoagulant regimens for CM prevention remains uncertain.
  
  
  METHODS
  A systematic review and meta-analysis were performed examining all randomized controlled trials (RCTs) assessing interventions acting via an anticoagulant mechanism compared with conventional care for the prevention of CM in adult patients receiving haemodialysis for end-stage kidney disease. Medline, EMBASE and the Cochrane Register were searched to November 2012. The primary outcome was CM. Secondary outcomes were CRB, all-cause mortality and bleeding events (all bleeding events reported or as defined by authors). Relative risks with 95% confidence intervals (CIs) for individual trials were pooled using random effects models for treatment classes.
  
  
  RESULTS
  The search yielded 28 trials including 3081 patients. Therapies assessed were alternative anticoagulant locking solutions (ALSs), systemic warfarin and low/no dose heparin locking solutions (normal saline locks). No significant effect on CM (18 trials, 1579 participants) was observed for alternative ALSs (9 trials, 887 participants, RR 0.85, 95% CI 0.68-1.07), or low/no dose heparin (4 trials, 231 participants, RR 0.99, CI 0.60-1.62), compared with heparin locking solutions (5000 units). Similarly, no significant effect was observed for warfarin (5 trials, 479 participants, RR 0.59, 95% CI 0.28-1.22) compared with placebo. No significant effect on CRB was observed (15 trials, 2367 participants) for alternative ALSs (11 trials, 2010 participants, RR 0.57, 95% CI 0.30-1.10), warfarin (1 trial, 174 participants, RR 2.40, 95% CI 0.88-6.52) or low/no dose heparin (3 trials, 183 participants, RR 0.76, 95% CI 0.35-1.64). All-cause mortality was not affected by alternative ALSs (9 trials, 1719 participants, RR 0.83, 95% CI 0.56-1.24) or warfarin (3 trials, 403 participants, RR 0.78, 95% CI 0.37-1.65). Bleeding events were only reported in seven trials, including only two trials of warfarin, with no clear effect demonstrated. Within the alternative ALSs group, the only agent with a reduction in CM was recombinant tissue plasminogen activator (rt-PA)-locking solution (RR 0.52, 95% CI 0.32-0.86) based on the results of a single trial. Trials were mainly of high risk of bias.
  
  
  CONCLUSIONS
  There is uncertainty on the benefits and harms of anticoagulant therapies over conventional care for prevention of CM. Further high-quality randomized trials, including safety outcomes, are needed.
authors.affiliation: Renal and Metabolic Division, The George Institute for Global Health, University of Sydney, Sydney, Australia.
authors.forename: Amanda Y
authors.initials: AY
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: Meg J
authors.initials: MJ
authors.lastname: Jardine
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage*; D002408:Catheters, Indwelling / Q000009:adverse effects*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D016032:Randomized Controlled Trials as Topic; D006435:Renal Dialysis / Q000009:adverse effects* / Q000295:instrumentation*; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants
keywords: alternative anticoagulant locking solutions; catheter malfunction; central venous haemodialysis catheters; low-dose heparin locking solutions; systematic review; warfarin