Use of fish oil supplements shows mixed results regarding graft patency for hemodialysis

CHICAGO – Among patients with new synthetic arteriovenous grafts (a synthetic tube grafted between an artery and vein) for vascular access for hemodialysis, daily ingestion of fish oil did not decrease the proportion of grafts with loss of patency (remaining open) within 12 months, according to a study in the May 2 issue of JAMA. However, fish oil recipients had a longer time without thrombosis (formation of a blood clot), half the thrombosis rate, and a clinically meaningful reduction in frequency of radiological and surgical interventions.

"Optimal hemodialysis requires reliable vascular access. Current options include the arteriovenous fistula [surgical creation of a connection between an artery and vein], synthetic arteriovenous graft, and central venous catheter, which in the United States are used in 55 percent, 21 percent, and 24 percent of prevalent patients receiving hemodialysis, respectively. The arteriovenous graft was the predominant vascular access type in North America during the early 1990s but fell out of favor owing to its high complication rates and associated costs. For example, thrombosis occurs in more than 50 percent of all arteriovenous grafts within 1 year after placement, necessitating a salvage procedure in more than 75 percent," according to background information in the article. To date, multiple interventions have failed to convincingly or consistently reduce thrombosis rates. Because of their antiproliferative, antioxidant, and vasodilatory (dilation) effects, the omega-3 fatty acids found in fish oils have theoretical appeal for preventing development of arteriovenous graft stenosis (narrowing) and thrombosis. A small, single-center prospective study of fish oil prophylaxis showed an improvement in 12-month graft patency.

Charmaine E. Lok, M.D., M.Sc., of the University of Toronto and Toronto General Hospital, and colleagues conducted a randomized controlled trial that compared arteriovenous graft patency and rates of thrombosis and intervention in patients with end-stage renal disease who received fish oil supplementation vs. placebo following creation of an arteriovenous graft. The study was conducted at 15 North American dialysis centers from November 2003 through December 2010, enrolling 201 adults with stage 5 chronic kidney disease (50 percent women, 63 percent white, 53 percent with diabetes), with follow-up for 12 months after graft creation. The participants were randomly allocated to receive fish oil capsules (four 1-gram capsules/day) or matching placebo on day 7 after graft creation. The primary outcome measure for the study was the proportion of participants experiencing graft thrombosis or radiological or surgical intervention during 12 months of follow-up.

The researchers found that there was no significant difference in the proportion of fish oil recipients and placebo recipients with loss of native patency (48 percent [48/99] vs. 62 percent [60/97], respectively. "However, the rate of these events was significantly lower in the fish oil group. The frequency of thrombosis events was reduced by half in the fish oil group, and the frequency of corrective interventions was lower."

The 12-month event-free rate (i.e., no loss of native patency of arteriovenous graft) was 48 percent in the fish oil group, compared with 32 percent in the placebo group. The reasons for arteriovenous graft loss were similar between treatment groups. The 12-month thrombosis-free rate was higher in the fish oil group (64 percent vs. 47 percent).

"Analysis of cardiovascular outcomes demonstrated superior cardiovascular event-free survival in the fish oil group. Compared with baseline, there were clinically significant reductions in systolic blood pressure at 6 months in the fish oil group that were sustained to 12 months," the authors write. "Sixty-four percent (63/99) of patients in the fish oil group compared with 42 percent (41/97) in the placebo group had at least 1 reduction in the dose or frequency of their antihypertensive medications."

"Although the risk of the primary end point was not significantly lower among fish oil recipients, this should be considered in the context of the apparent consistent clinical benefits observed for the secondary outcomes."

The researchers note that the use of arteriovenous grafts has declined over the last 10 years, largely driven by the emphasis on use of fistulas. "Arteriovenous grafts may be suitable for patients receiving hemodialysis whose veins are unsuitable for fistula creation or who have experienced prior problems with fistula nonmaturation. However, compared with functioning fistulas, arteriovenous grafts may require a 3- to 4-fold higher frequency of interventions to maintain equivalent long-term patency. Identification of safe and inexpensive agents that prolong arteriovenous graft patency and reduce the frequency of interventions to salvage graft complications might encourage increased use of grafts."

(JAMA. 2012;307[17]:1809-1816. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

In an accompanying editorial, Bradley S. Dixon, M.D., of the University of Iowa, Iowa City, addresses the question of whether clinicians, based on these findings, should consider increasing the use of hemodialysis grafts accompanied by the administration of fish oil and an antiplatelet agent to prolong graft patency.

"Thus far, the available data do not support this approach. Despite the reduction in the rate of graft thrombosis and angioplasty procedures with fish oil, the rate of these events is still lower with arteriovenous fistulas, and fistulas remain the preferred means of hemodialysis access. However, if a patient cannot obtain a fistula and requires a graft, use of fish oil and an antiplatelet agent appears reasonable, pending the results of further studies."

(JAMA. 2012;307[17]:1859-1860. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: Please see the article for additional information, including financial disclosures, funding and support, etc.

To contact Charmaine E. Lok, M.D., M.Sc., call Jim Oldfield at 416-946-8423 or email jim.oldfield@utoronto.ca. To contact editorial author Bradley S. Dixon, M.D., call Tom Moore at 319-356-3945 or email thomas-moore@uiowa.edu.