Fish Oil in Dialysis: Check the Secondary Outcomes

Jeffrey S. Berns, MD


June 13, 2012

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Hello. This is Jeffrey Berns, Editor-in-Chief of Medscape Nephrology. I want to talk in detail today about a study that I mentioned briefly more than a year ago, when it was presented at the American Society of Nephrology Annual Meeting. It was recently published in the May 2, 2012, issue of JAMA, revealing the results of the FISH trial.[1] I congratulate Dr. Charmaine Lok and her colleagues for conducting such a nice study.

This was a randomized, controlled, double-blind trial comparing 4 g of fish oil per day with placebo in patients who were receiving new hemodialysis synthetic grafts. The graft was either the first-ever graft (before dialysis) or a new graft in a patient who had already been on dialysis for some time.

The fish oil capsules contained isopentanoic acid and docosahexaenoic acid, which are typical compounds found in fish oil supplements. Patients took 4 capsules per day starting 1 week after the graft was implanted. This was a multicenter study conducted in Canada and the United States. Most of the patients had forearm grafts, but some had upper-arm grafts and a few even had leg grafts. About one half of the patients were diabetic, about one half were taking aspirin, about one quarter were on warfarin, and about 10%-12% were on clopidogrel.

The primary outcome of interest was the proportion of patients with graft thrombosis or requiring an intervention during 1 year of follow-up. This endpoint was not statistically significant, although there was a strong trend in this direction, with a risk ratio of 0.78 -- suggestive of a 22% reduction, with 62% of control patients and 48% of fish oil patients having either a thrombosis or the need for intervention.

Secondary outcomes looking at the success of the fish oil preparation were statistically significant, showing a lower rate of overall graft failure, with one half as many thrombotic events and a significantly higher primary patency rate. There was a strong suggestion of benefit in terms of graft patency, even though the primary outcome was not statistically significant.

Interestingly, there was also a 57% reduction in cardiovascular events, a 5-mm Hg reduction in systolic blood pressure, and a reduction in the number of antihypertensive medications required to control blood pressure.

Overall, I was very impressed by the study despite the absence of statistical significance in the primary outcome. The other outcomes were statistically significant and, overall, highly suggestive of a benefit on hemodialysis grafts, with added cardiovascular benefits as well.

Many questions were raised by the study. One wonders whether a more potent preparation or fewer capsules at lower doses would still be successful, particularly if it was started prior to surgery. However, there was an anticoagulant effect that was of concern and was the reason for starting the regimen after surgery. We don't know whether other formulations of fish oil would confer the same benefit or whether a combination of fish oil with aspirin or other antiplatelet therapies would be even more successful. Another question that might be asked is whether fish oil would be a benefit simply by reducing restenosis after a dialysis graft stenosis angioplasty.

Taking 4 capsules per day is a significant pill burden, but it certainly seems worth considering in dialysis patients for preventing graft thrombosis and conferring some additional cardiovascular benefit.

I'm sure that we will see more studies about this. I think this is a very important and very significant study. Again, I congratulate Dr. Lok and her colleagues for conducting such a nice study. I hope you read it. It's in the May 2, 2012, issue of JAMA.

I'm Jeffrey Berns, Editor-in-Chief of Medscape Nephrology. Thanks for listening.