Dr Patrick Gladding on EPA (fish oil) and Triglycerides

Author: Dr Patricia Ding

Transcript:

Dr Patricia Ding:

I'm Patricia Ding, cardiologist. I'm here today with Dr. Patrick Gladding. Hi Patrick.

Dr Patrick Gladding:

Hi, everyone. Hi, Patricia.

Dr Patricia Ding:

Okay, right. So can you tell us about the topic today?

Dr Patrick Gladding:

So I'm just going to talk to you about triglycerides. It's an area that's often been ignored. And I think the main reason is until now we didn't realize that triglycerides were important. We often see them as elevated in people with diabetes, obesity, metabolic syndrome, but we don't really know how important they are and what we should do about them. So it wasn't until the genomic studies came along that we realized that things like HDL, which we call, normally, good cholesterol, are actually noncausal. So they don't have a strong relationship with cardiovascular disease in themselves. It's the relationship with triglycerides that's important.

Dr Patricia Ding:

Yeah. And most of the time over the last, what, 20 decades, we've put emphasis on reducing LDL to get optimal cardiovascular outcome. But triglyceride, we will treat the number sometimes, but we're not as aggressive as treating LDL levels.

Dr Patrick Gladding:

Yeah, absolutely. We've done a lot of trials in cardiology looking to raise HDL, and they've all failed, essentially because of the issue around HDL being not the most important lipid molecule. LDL still is the most important, but triglycerides are up there in terms of level of important. There's lots of lipid particles that are also pro-atherogenic that we don't measure that have triglycerides in them. So it is important to get the triglycerides down. And the main way we do that still is with statins. Then we have fibrates. But the most exciting thing are these new EPA-only fish oils that really... That's the main reason for talking today about.

Dr Patricia Ding:

Yeah. So tell us about EPA and what is the dosage that's used in the trial at the moment?

Dr Patrick Gladding:

Yeah, so the dose is generally pretty high. I think to start off with, there has to be a distinction between what a standard fish oil is and what an EPA-only fish oil is. Over the counter, most of the fish oils you buy have both EPA, which is eicosapentaenoic acid, and docosahexaenoic acid, that's DHA. There was a study many years ago called JELIS, which was done in Japan. It's J-E-L-I-S.

Dr Patricia Ding:

Yes, I saw that, yeah.

Dr Patrick Gladding:

And that showed quite good benefits to people who were taking EPA-only fish oils. In New Zealand, we participated in a multicenter trial called REDUCE-IT, which was run out of Harvard. And it showed, that in a large population of patients with established cardiovascular disease or diabetes, that lowering triglycerides with EPA-only fish oils had quite a significant benefit.

Dr Patricia Ding:

Right. Okay. All right. So can you tell us about the REDUCE trial? What is the design of the trial and what are the endpoints?

Dr Patrick Gladding:

Yeah, so it was a randomized controlled trial. It was a multicenter study. As I mentioned, there were New Zealanders in this study too, but it was run out of the US. It enrolled around 5,000 patients randomized to placebo. Now, the placebo was a mineral oil so there was some question about whether the mineral oil was actually a negative effect and made the EPA fish oil look good. But in any case, that debate's ongoing. The outcomes were measured over five years, and they're all the standard ones, so cardiovascular outcomes, cardiovascular death, all cause death, and measured triglycerides and lipids.

Dr Patricia Ding:

And the trial was done on mostly people with confirmed diagnosis with coronary artery disease and they're already on statin?

Dr Patrick Gladding:

That's right, yeah. They're all on effective lipid-lowering therapy already, so this was like you say, add on to established therapies.

Dr Patricia Ding:

Right. And what was the outcome of the trial?

Dr Patrick Gladding:

The outcome was excellent across all the outcome measures. There were significantly reduced numbers of myocardial infarction, cardiovascular death, and reduced revascularization rates as well, so actually less PCI being done in the treatment arm of the study.

Dr Patricia Ding:

Right, okay. By 25%.

Dr Patrick Gladding:

Yeah, absolutely. Quite a considerable amount and with a very, very big p-value or very small p-value, depending on how you look at it.

Dr Patricia Ding:

All right. Okay. So how do we translate that to our clinical practice in the future?

Dr Patrick Gladding:

At the moment the, EPO fish oil used in that trial, it's called Vascepa. It's available only in the United States. It's an expensive... I believe around $300 a month there.

Dr Patricia Ding:

Wow.

Dr Patrick Gladding:

Which is a lot, because most fish oils really shouldn't be more than 40 to $60 a month. The festival that used was very specific and it's not yet known whether you can generalize to other EPA-only fish oils, but you probably can. And there are others that are out there that are available online that only contain EPA, that also lower triglycerides and probably have the same effect. The other bit of good news is that the company... well, not good news for the company making this, but they've lost their patents, which means there'll be generics on the market very soon. So keep your eyes peeled for EPA-only fish oils to treat triglycerides.

Dr Patricia Ding:

Yeah. We'll have to really look carefully on the bottle...

Dr Patrick Gladding:

On the bottle.

Dr Patricia Ding:

... the actual ingredients in the fish oil.

Dr Patrick Gladding:

Yeah, right. And we don't know yet what it is about EPA. And it's not that DHA is bad, but it's something to do with the ratios and the dominance of one over the other, I think.

Dr Patricia Ding:

Right. And hopefully we get some long-term results out that will guide us to give a target for treating the triglyceride level to improve cardiovascular outcome as well.

Dr Patrick Gladding:

Absolutely. We don't have... With LDL cholesterol, it's quite clear to us what's high, what's considered very high.

Dr Patricia Ding:

In fact, I think the LDL target nowadays is so low, 1.4, it's getting to the point of slightly being inaccurate, because the really low LDL is less accurate than sort of medium range. So the body has to use the total minus the HDL.

Dr Patrick Gladding:

Yeah, right. Yeah, absolutely. The sensitivity and precision of these things becomes less than...

Dr Patricia Ding:

I think this is one area to look out for in the aggressive risk factor management for cardiovascular health.

Dr Patrick Gladding:

Yeah, right. I mean, triglycerides being high, above nine, there's also a risk for pancreatitis. And as you know, that's a medical emergency. So lowering triglycerides above that level's obviously really important. Yeah, in the future, hopefully there'll be more information about what numbers to treat to and to benefit our patients.

Dr Patricia Ding:

All right. Okay, thank you very much, Patrick.

Dr Patrick Gladding:

Thanks, Patricia.

 

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