Andrea K. Viecelli

Effect of Fish Oil Supplementation and Aspirin Use on Arteriovenous Fistula Failure in Patients Requiring Hemodialysis: A Randomized Clinical Trial

Importance Vascular access dysfunction is a leading cause of morbidity and mortality in patients requiring hemodialysis. Arteriovenous fistulae are preferred over synthetic grafts and central venous catheters due to superior long-term outcomes and lower health care costs, but increasing their use is limited by early thrombosis and maturation failure. &ohgr;-3 Polyunsaturated fatty acids (fish oils) have pleiotropic effects on vascular biology and inflammation and aspirin impairs platelet aggregation, which may reduce access failure. Objective To determine whether fish oil supplementation (primary objective) or aspirin use (secondary objective) is effective in reducing arteriovenous fistula failure. Design, Setting, and Participants The Omega-3 Fatty Acids (Fish Oils) and Aspirin in Vascular Access Outcomes in Renal Disease (FAVOURED) study was a randomized, double-blind, controlled clinical trial that recruited participants with stage 4 or 5 chronic kidney disease from 2008 to 2014 at 35 dialysis centers in Australia, Malaysia, New Zealand, and the United Kingdom. Participants were observed for 12 months after arteriovenous fistula creation. Interventions Participants were randomly allocated to receive fish oil (4 g/d) or matching placebo. A subset (n = 406) was also randomized to receive aspirin (100 mg/d) or matching placebo. Treatment started 1 day prior to surgery and continued for 12 weeks. Main Outcomes and Measures The primary outcome was fistula failure, a composite of fistula thrombosis and/or abandonment and/or cannulation failure, at 12 months. Secondary outcomes included the individual components of the primary outcome. Results Of 1415 eligible participants, 567 were randomized (359 [63%] male, 298 [53%] white, 264 [47%] with diabetes; mean [SD] age, 54.8 [14.3] y). The same proportion of fistula failures occurred in the fish oil and placebo arms (128 of 270 [47%] vs 125 of 266 [47%]; relative risk [RR] adjusted for aspirin use, 1.03; 95% CI, 0.86-1.23; P = .78). Fish oil did not reduce fistula thrombosis (60 [22%] vs 61 [23%]; RR, 0.98; 95% CI, 0.72-1.34; P = .90), abandonment (51 [19%] vs 58 [22%]; RR, 0.87; 95% CI, 0.62-1.22; P = .43), or cannulation failure (108 [40%] vs 104 [39%]; RR, 1.03; 95% CI, 0.83-1.26; P = .81). The risk of fistula failure was similar between the aspirin and placebo arms (87 of 194 [45%] vs 83 of 194 [43%]; RR, 1.05; 95% CI, 0.84-1.31; P = .68). Conclusions and Relevance Neither fish oil supplementation nor aspirin use reduced failure of new arteriovenous fistulae within 12 months of surgery. Trial Registration anzctr.org.au Identifier: CTRN12607000569404

The pathogenesis of hemodialysis vascular access failure and systemic therapies for its prevention: Optimism unfulfilled

In patients receiving hemodialysis, the provision of safe and effective vascular access using an arteriovenous fistula or graft is regarded as a critical priority by patients and health professionals. Vascular access failure is associated with morbidity and mortality, such that strategies to prevent these outcomes are essential. Inadequate vascular remodeling and neointimal hyperplasia resulting in stenosis and frequently thrombosis are critical to the pathogenesis of access failure. Systemic medical therapies with pleiotropic effects including antiplatelet agents, omega‐3 polyunsaturated fatty acids (fish oils), statins, and inhibitors of the renin‐angiotensin‐aldosterone system (RAAS) may reduce vascular access failure by promoting vascular access maturation and reducing stenosis and thrombosis through antiproliferative, antiaggregatory, anti‐inflammatory and vasodilatory effects. Despite such promise, the results of retrospective analyses and randomized controlled trials of these agents on arteriovenous fistula and graft outcomes have been mixed. This review describes the current understanding of the pathogenesis of arteriovenous fistula and graft failure, the biological effects of antiplatelet agents, fish oil supplementation, RAAS blockers and statins that may be beneficial in improving vascular access survival, results from clinical trials that have investigated the effect of these agents on arteriovenous fistula and graft outcomes, and it explores future therapeutic approaches combining these agents with novel treatment strategies.

Clinicians’ and researchers’ perspectives on establishing and implementing core outcomes in haemodialysis: semistructured interview study

Objectives To describe the perspectives of clinicians and researchers on identifying, establishing and implementing core outcomes in haemodialysis and their expected impact. Design Face-to-face, semistructured interviews; thematic analysis. Stetting Twenty-seven centres across nine countries. Participants Fifty-eight nephrologists (42 (72%) who were also triallists). Results We identified six themes: reflecting direct patient relevance and impact (survival as the primary goal of dialysis, enabling well-being and functioning, severe consequences of comorbidities and complications, indicators of treatment success, universal relevance, stakeholder consensus); amenable and responsive to interventions (realistic and possible to intervene on, differentiating between treatments); reflective of economic burden on healthcare; feasibility of implementation (clarity and consistency in definition, easily measurable, requiring minimal resources, creating a cultural shift, aversion to intensifying bureaucracy, allowing justifiable exceptions); authoritative inducement and directive (endorsement for legitimacy, necessity of buy-in from dialysis providers, incentivising uptake); instituting patient-centredness (explicitly addressing patient-important outcomes, reciprocating trial participation, improving comparability of interventions for decision-making, driving quality improvement and compelling a focus on quality of life). Conclusions Nephrologists emphasised that core outcomes should be relevant to patients, amenable to change, feasible to implement and supported by stakeholder organisations. They expected core outcomes would improve patient-centred care and outcomes.

Omega-3 Polyunsaturated Fatty Acid Supplementation to Prevent Arteriovenous Fistula and Graft Failure: A Systematic Review and Meta-analysis of Randomized Controlled Trials

BACKGROUND Arteriovenous access failure frequently occurs in people on hemodialysis and is associated with morbidity, mortality and large healthcare expenditures. Omega-3 polyunsaturated fatty acids (omega-3 PUFA) may improve access outcomes via pleiotropic effects on access maturation and function, but may cause bleeding complications. STUDY DESIGN Systematic review with meta-analysis. SETTING & POPULATION Adults requiring hemodialysis via arteriovenous fistula or graft. SELECTION CRITERIA Trials evaluating omega-3 PUFA for arteriovenous access outcomes identified by searches in CENTRAL, MEDLINE, and Embase to 24 January 2017. INTERVENTION Omega-3 PUFA. OUTCOMES Primary patency loss, dialysis suitability failure, access abandonment, interventions to maintain patency or assist maturation, bleeding, gastrointestinal side-effects, all-cause and cardiovascular mortality, hospitalization, and treatment adherence. Treatment effects were summarized as relative risks (RR) and 95% confidence intervals (CI). Evidence was assessed using GRADE. RESULTS Five eligible trials (833 participants) with a median follow-up of 12 months compared peri-operative omega-3 PUFA supplementation with placebo. One trial (n=567) evaluated treatment for fistulae and four (n=266) for grafts. Omega-3 PUFA supplementation prevented primary patency loss with moderate certainty (761 participants, RR 0.81, CI 0.68-0.98). Low quality evidence suggested, that omega-3 PUFA may have had little or no effect on dialysis suitability failure (536 participants, RR 0.95, CI 0.73-1.23), access abandonment (732 participants, RR 0.78, CI 0.59-1.03), need for interventions (732 participants, RR 0.82, CI 0.64-1.04), or all-cause mortality (799 participants, RR 0.99, CI 0.51-1.92). Bleeding risk (793 participants, RR 1.40, CI 0.78-2.49) or gastrointestinal side-effects (816 participants, RR 1.22, CI 0.64-2.34) from treatment were uncertain. There was no evidence of different treatment effects for grafts and fistulae. LIMITATIONS Small number and methodological limitations of included trials. CONCLUSIONS Omega-3 PUFA supplementation probably protects against primary loss of arteriovenous access patency, but may have little or no effect on dialysis suitability failure, access interventions or access abandonment. Potential treatment harms are uncertain.

Updates on Baseline characteristics of the omega-3 fatty acids (Fish oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study.

The Fish oils and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) trial investigated whether 3 months of omega‐3 polyunsaturated fatty acids, either alone or in combination with aspirin, will effectively reduce primary access failure of de novo arteriovenous fistulae. This report presents the baseline characteristics of all study participants, examines whether study protocol amendments successfully increased recruitment of a broader and more representative haemodialysis cohort, including patients already receiving aspirin, and contrasts Malaysian participants with those from Australia, New Zealand and the United Kingdom (UK).

Outcomes of the First and Second Hemodialysis Fistula: A Cohort Study

RATIONALE & OBJECTIVE Fistulas are the preferred form of hemodialysis access; however, many fistulas fail to mature into usable accesses after creation. Data for outcomes after placement of a second fistula are limited. STUDY DESIGN Cohort study. SETTING & PARTICIPANTS People who initiated hemodialysis therapy in any of 5 Canadian dialysis programs (2004-2012) and had at least 1 hemodialysis fistula placed. PREDICTOR Second versus initial fistula; receipt of 2 versus 1 fistula; second versus first fistula in recipients of 2 fistulas. OUTCOMES Catheter-free fistula use during 1 year following initiation of hemodialysis therapy or following fistula creation, if created after hemodialysis therapy start; proportion of time with catheter-free use; time to catheter free use; time of functional patency. ANALYTICAL APPROACH Logistic regression; fractional regression. RESULTS Among the 1,091 study participants (mean age, 64±15 [SD] years; 63% men; 59% with diabetes), 901 received 1 and 190 received 2 fistulas. 38% of second fistulas versus 46% of first fistulas were used catheter free at least once. Average percentages of time that second and initial fistulas were used catheter free were 34% and 42%, respectively (OR, 0.72; 95% CI, 0.54-0.94). Compared with people who received 1 fistula, those who received 2 fistulas were less likely to achieve catheter-free use (26% vs 56%) and remain catheter free (23% vs 49% of time; OR, 0.30, 95% CI, 0.24-0.39). Among people who received 2 fistulas, the proportion of time that the second fistula was used catheter free was 11% higher with each 10% greater proportion of time that the first fistula was used catheter free (95% CI, 1%-22%). Model discrimination was modest (C index, 0.69). LIMITATIONS Unknown criteria for patient selection for 1 or 2 fistulas; unknown reasons for prolonged catheter use. CONCLUSIONS Outcomes of a second fistula may be inferior to outcomes of the initial fistula. First and second fistula outcomes are weakly correlated and difficult to predict based on clinical characteristics.

Effect of fish oil and aspirin on arteriovenous fistula failure in haemodialysis - a randomized controlled trial

EFFECT OF FISH OIL AND ASPIRIN ON ARTERIOVENOUS FISTULA FAILURE IN HAEMODIALYSIS – A RANDOMIZED CONTROLLED TRIAL IRISHA,VIECELLIA, HAWLEYC, HOOI L, PASCOEE, PAUL-BRENT P, BADVE S, MORI T, CASS A, KERR P, VOSS D, ONG L, POLKINGHORNE K, for the Omega-3 Fatty Acids (Fish Oils) and Aspirin in Vascular Access Outcomes in Renal Disease (FAVOURED) Study Collaborative Group. Department of Nephrology Fiona Stanley Hospital, Perth, Australia, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia, Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia, Australasian Kidney Trials Network, School of Medicine, University of Queensland, Brisbane, Australia, Department of Medicine and Hemodialysis Unit, Hospital Sultanah Aminah, Johor Bahru, Malaysia, Department of Nephrology, St George Hospital, Sydney, Australia, The George Institute for Global Health, Sydney, Australia, Menzies School of Health Research, Charles Darwin University, Darwin, Australia, Department of Nephrology, Monash Medical Centre, Melbourne, Australia, Department of Medicine, Monash University, Melbourne, Australia, Middlemore Renal Services, Middlemore Hospital, Auckland, New Zealand, Department of Nephrology, Penang Hospital, Georgetown, Malaysia, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia

A comparison of arteriovenous fistula failure between Malaysian and Australian and New Zealand participants enrolled in the favoured trial

D’EMDEN M, FITCHETT D, GILJANOVIC KÎS S, WOERLE H, ZINMAN B, INZUCCHI S University of Queensland, Australia, St Michael’s Hospital, Division of Cardiology, University of Toronto, Toronto, Canada, Eli Lilly (Suisse) S.A., Representative Office, Zagreb, Croatia, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada, Division of Endocrinology, University of Toronto, Toronto, Canada, Section of Endocrinology, Yale University School of Medicine, New Haven, United States of America