Date Published: March 26, 2019
Publisher: Public Library of Science
Author(s): Andrea K. Viecelli, Kevan R. Polkinghorne, Elaine M. Pascoe, Peta-Anne Paul-Brent, Carmel M. Hawley, Sunil V. Badve, Alan Cass, Lai-Seong Hooi, Peter G. Kerr, Trevor A. Mori, Loke-Meng Ong, David Voss, David W. Johnson, Ashley B. Irish, Iratxe Puebla.
Arteriovenous fistulas (AVF) for haemodialysis often experience early thrombosis and maturation failure requiring intervention and/or central venous catheter (CVC) placement. This secondary and exploratory analysis of the FAVOURED study determined whether omega-3 fatty acids (fish oils) or aspirin affected AVF usability, intervention rates and CVC requirements.
In 567 adult participants planned for AVF creation, all were randomised to fish oil (4g/d) or placebo, and 406 to aspirin (100mg/d) or placebo, starting one day pre-surgery and continued for three months. Outcomes evaluated within 12 months included AVF intervention rates, CVC exposure, late dialysis suitability failure, and times to primary patency loss, abandonment and successful cannulation.
Final analyses included 536 participants randomised to fish oil or placebo (mean age 55 years, 64% male, 45% diabetic) and 388 randomised to aspirin or placebo. Compared with placebo, fish oil reduced intervention rates (0.82 vs 1.14/1000 patient-days, incidence rate ratio [IRR] 0.72, 95% confidence interval [CI] 0.54–0.97), particularly interventions for acute thrombosis (0.09 vs 0.17/1000 patient-days, IRR 0.53, 95% CI 0.34–0.84). Aspirin significantly reduced rescue intervention rates (IRR 0.45, 95% CI 0.27–0.78). Neither agent significantly affected CVC exposure, late dialysis suitability failure or time to primary patency loss, AVF abandonment or successful cannulation.
Although fish oil and low-dose aspirin given for 3 months reduced intervention rates in newly created AVF, they had no significant effects on CVC exposure, AVF usability and time to primary patency loss or access abandonment. Reduction in access interventions benefits patients, reduces costs and warrants further study.
A functioning vascular access is essential for patients requiring haemodialysis (HD). A native arteriovenous fistula (AVF) has the best long-term outcomes although this advantage is frequently limited by early thrombosis, maturation failure, the need for access interventions and/or placement of a central venous catheter (CVC)[1,2]. Vascular access interventions are burdensome for patients and incur significant health care costs. Patients and health professionals consider the need for interventions to maintain the use of a vascular access for HD the most important adverse outcome of a vascular access, yet treatments to reduce intervention rates and to increase the usability of AVF have not been a major focus of randomised trials in patients requiring HD. The inhibitory effects of omega-3 polyunsaturated fatty acids (fish oils) on platelet aggregation[6,7], inflammation[8,9], and neointimal hyperplasia, and of aspirin on platelet inhibition could be beneficial in reducing the need for interventions for acute thrombosis and maturation-enhancing procedures. Fish oil supplementation has been shown to reduce intervention and thrombosis rates in arteriovenous grafts but has not previously been studied in AVF.
The FAVOURED study randomised 567 participants to fish oil or placebo from August 21, 2008 to February 28, 2014, of which 536 were included in the final analysisFig 1. Table 1 shows the baseline characteristics of the 536 participants; 31 participants were excluded because they either died prior to being assessed on any outcome (n = 5 in each of the fish oil and placebo groups) or did not have an AVF created (n = 9 randomised to fish oil, n = 12 randomised to placebo). Participants had a mean age of 55 years and 64% were male. Baseline characteristics were generally well balanced although more participants treated with fish oil compared to placebo were diabetic (48% versus 43%) or smokers (53% versus 48%). At study initiation, 49% were on dialysis with 84% dialysing through a CVC. At study end, 83% received dialysis with 61% using the study AVF (167 [62%] randomised to fish oil, 159 [60%] randomised to placebo).
Secondary and exploratory outcome analyses of the FAVOURED trial showed that a quarter of participants required at least one AVF intervention within the first year of AVF creation, almost 30% experienced primary patency loss and 50% required at least one CVC. Three months of fish oil supplementation reduced the rate of AVF interventions, principally driven by a 47% relative reduction in rescue procedures for acute thrombosis. Similarly, low-dose aspirin reduced the incidence of rescue interventions by 55%. However, neither fish oil nor aspirin was effective in reducing the frequency and duration of CVC use, the frequency of late dialysis suitability failure or the time to first successful cannulation. Similarly, the time to first AVF intervention, primary patency loss or AVF abandonment did not differ significantly between treatment groups.