Fish Oil, Aspirin Do Not Lower AVF Failure Risk in Dialysis

Ricki Lewis, PhD

January 10, 2017

Neither omega-3 fatty acids from fish nor aspirin prevented failure of arteriovenous fistulae (AVFs) in patients receiving hemodialysis, according to results of a new study published online January 3 in JAMA Internal Medicine.

Ashley B. Irish, MD, from the Department of Nephrology at Fiona Stanely Hospital and the University of Western Australia in Perth, and colleagues used the measure of whether AVFs created for hemodialysis failed as a way of testing the protective effects of omega-3 fatty acid supplementation.

AVFs are safer than synthetic grafts or central venous catheters, but failure rates are 20% to 50% as a result of thrombosis or failure of the fistulae to "mature" fast enough. In addition, AVF failure is a major cause of morbidity and mortality in patients receiving hemodialysis.

Supplementation with omega-3 fatty acids could facilitate creation of safe AVFs in several ways: promoting vasodilation and red blood cell flexibility, reducing blood viscosity and inflammation, and inhibiting platelet aggregation and smooth muscle cell proliferation, the authors suggest.

However, neither fish oil nor aspirin has previously been evaluated for preventing or lowering the risk for AVF failure in patients receiving dialysis.

In an accompanying editorial, Gregory Curfman, MD, from Harvard Medical School, Boston, Massachusetts, writes: "The [AVF], as a direct surgical anastomosis between artery and vein, is a model vascular system, and the lack of benefit of a relatively high dose of fish oil in preventing thrombosis or preserving patency provides negative data in this specific form of vascular pathobiologic disease."

Conflicting Prior Findings With Fish Oils for CVD Prevention

Several clinical trials have generated conflicting findings about the effect of dietary supplementation with omega-3 fatty acids (eicosapentaenoic acid and docosahexanoic acid) on secondary prevention after cardiovascular disease.

Open-label, nonplacebo-controlled studies demonstrated a 15% decrease in cardiovascular events among patients who had myocardial infarction (GISSI, Prevenzione Study, 1999) and a 19% decrease in major coronary events among patients with hypercholesterolemia (Japan Eicosapentanoic Acid Lipid Intervention Study, 2007). In addition, the randomized, double-blind GISSI Heart Failure Study (2008) indicated a 9% decline in overall mortality in patients who had heart failure and received omega-3 fatty acid supplementation.

However, more recent double-blind assessments have indicated no benefit in secondary prevention of cardiovascular disease after omega-3 fatty acid supplementation, and a meta-analysis that included more than 20,000 patients confirmed the lack of effect.

No Clinically Relevant Effect of Fish Oil on AVF Failure

In this current study, the Omega-3 Fatty Acids (Fish Oils) and Aspirin in Vascular Access Outcomes in Renal Disease (FAVOURED) trial, Dr Irish and colleagues set out to assess the role of 4 g/day fish oils to reduce failure of AVFs created for hemodialysis in patients with stage 4 or 5 chronic kidney disease.

The randomized, double-blind, placebo-controlled trial recruited 567 adults at 35 hemodialysis centers in the United Kingdom, New Zealand, Malaysia, and Australia from 2008 to 2014, including 536 patients in the final analysis.

At first, patients were assessed only at 12 weeks for early thrombosis in the AVF, but the investigators broadened that to "AVF access failure at 12 months after fistula creation," which also included analysis of abandonment and/or cannulation failure. Efficacy of fish oil was the primary objective, and that of aspirin the secondary objective.

Of the 270 participants randomly assigned to receive fish oil, 128 (47%) experienced AVF failure, as did 125 (47%) of 266 assigned to placebo (relative risk [RR] adjusted for aspirin use, 1.03; P = .78).

Analysis of specific events yielded similar findings: thrombosis (60 [22%] vs 61 [23%]; adjusted RR, 0.98; P = .90), AVF abandonment (51 [19%] vs 58 [22%]; RR, 0.87; P = .43), and cannulation failure (108 [40%] vs 104 [39%]; RR, 1.03; P = .81).

A significant difference in effect of fish oil on AVF failure did emerge among patients who also had diabetes mellitus, however (P = .03 for interaction; RR, 1.30 vs 0.85).

Results for aspirin use were similar to those for fish oil; that is, there was no apparent effect. Risk for AVF failure was 87 (45%) vs 83 (43%; RR, 1.05; P = .68) for aspirin vs placebo, respectively.

The findings also did not reveal an effect of aspirin compared with placebo on the components of AVF failure (thrombosis, 38 [20%] vs 35 [18%]; RR, 1.09; P = .70), AVF abandonment (46 [24%] vs 35 [18%]; RR, 1.31; P = .17), or cannulation failure (73 [38%] vs 74 [38%]; RR, 0.99; P = .92)

The researchers conclude that "a clinically relevant effect of fish oil on AVF failure was not demonstrated."

A limitation of the study may have been the brevity of fish oil supplementation (3 months), the researchers note, but they chose this endpoint because AVFs typically mature or fail in this timeframe. The aspirin dose may also have been too low, they suggest.

However, they caution that the investigation did not reveal the mechanism behind the lack of efficacy.

Still, the high failure rate "remains the most important impediment to successful hemodialysis and is considered a critical priority by patients and clinicians," they observe.

Eight coauthors report receiving grant funding from Abbott Products Operations A and Amgen Australia Pty Ltd.

JAMA Intern Med. Published online January 3, 2017. Article abstract, Editorial extract

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