Strategies to improve vascular access outcomes in haemodialysis patients

Abstract

It is estimated that over 3 million people worldwide are currently treated for end-stage kidney disease, with most receiving haemodialysis (HD). A functioning vascular access (VA) provides a lifeline for patients requiring HD but VA dysfunction remains one of the leading causes of excessive morbidity, mortality and healthcare costs in this group. Despite increasing numbers of VA trials, successful interventions to improve VA outcomes have been sparse and compromised by highly variable, often selectively reported outcomes of limited relevance to patients and health professionals.This thesis aimed to establish strategies to improve VA outcomes by 1) determining whether fish oil or aspirin is effective in improving outcomes of newly created arteriovenous fistulas (AVFs); and, 2) establishing a standardised core outcome measure for VA based on the shared priorities of patients and health professionals to improve the consistency, reliability and relevance of VA research in HD.Aim 1 was addressed with an international, double-blind, randomised, placebo-controlled trial entitled, “omega-3 fatty acids (Fish oils) and Aspirin in Vascular access OUtcomes in REnal Disease” (FAVOURED). It included 567 adult participants planned for AVF creation who were randomised to fish oil (4g/d) or placebo. Of these, 406 participants were also randomised to aspirin (100mg/d) or placebo. Treatment started 1 day pre-surgery and was continued for 12 weeks. The primary outcome was AVF failure (a composite of thrombosis and/or abandonment and/or cannulation failure) at 12 months. Secondary outcomes included the primary outcome components, AVF interventions, and central venous catheter (CVC) requirement. The FAVOURED study revealed that 12 weeks of fish oil did not reduce the proportion of AVF failure compared to placebo (47% versus 47%, relative risk [RR] adjusted for aspirin use 1.03, 95% confidence interval [CI] 0.86-1.23) or its outcome components. Low-dose aspirin was similarly ineffective. However, fish oil was effective in reducing AVF intervention rates (0.82 vs 1.14 interventions/1000 patient-days, incident rate ratio [IRR] 0.72, 95% CI 0.54-0.97), driven by a significant relative reduction in rescue interventions for thrombosis by 47%. Similarly, low-dose aspirin significantly reduced rescue intervention rates by 55%. Neither fish oil nor aspirin reduced the frequency or duration of CVC requirements compared to placebo.FAVOURED trial results were then included in a meta-analysis of randomised controlled trials (RCTs) to determine the efficacy and safety of fish oil supplementation to prevent complications of arteriovenous fistulas and grafts. Based on meta-analysis of five RCTs (833 participants) comparing fish oil supplementation with placebo, fish oil prevented primary patency loss with moderate certainty (761 participants, RR 0.81, CI 0.68-0.98) but may have had little or no effect on other VA outcomes or mortality and uncertain effects on bleeding risk and gastrointestinal side-effects. No treatment effect differences were observed between grafts and fistulas.Aim 2 was achieved through the global Standardised Outcomes in NephroloGy (SONG) Initiative, which aims to establish core outcomes that are critically important to patients with kidney disease and health professionals using a multi-step evidence- and consensus-based process. Vascular access was identified as one of four core outcome domains for haemodialysis along with cardiovascular disease, fatigue and death. The core outcome measure for VA was established by initially conducting a systematic review of 168 RCTs that identified 23 VA outcomes, based on more than 1400 outcome measures. Vascular access function was the most frequently reported outcome (81% of trials) followed by infection (38%). A subsequent multi-language survey completed by 873 participants (26% patients/caregivers and 74% health professionals) from 58 countries confirmed function to be the top critically important outcome. Themes from this survey and an international multi-stakeholder consensus workshop indicated that function was considered the core outcome for VA based on its broad applicability to all access types and its critical impacts on quality of life, survival and various access-related outcomes. ‘The rate of interventions to maintain VA use for HD’ was considered a pragmatic and feasible outcome measure for VA function that was meaningful to patients and clinicians. The feasibility and reliability of this proposed core outcome measure will now be assessed in an international, prospective validation study to facilitate global implementation in research and clinical practice.In conclusion, the FAVOURED study found that neither fish oil nor aspirin significantly reduced the primary binary composite outcome of AVF failure, but that each agent may reduce intervention rates in newly created AVFs. Through the SONG initiative, function defined by intervention rate was found to be the most important VA outcome based on the shared priorities of patients and health professionals. Consistent reporting of VA function in all studies in haemodialysis through global implementation of the SONG VA core outcome will maximise the opportunity to further explore and either confirm or refute the possible treatment benefits of fish oil or aspirin in improving VA function. It will also help to foster discovery of other effective interventions for improving VA function in HD patients.