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

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. OBJECTIVES: 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). SEARCH 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN 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. AUTHORS' 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.

Anticoagulant therapies for the prevention of intravascular catheters malfunction in patients undergoing haemodialysis: systematic review and meta-analysis of randomized, controlled trials.

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.