Tag Archive for: Vascepa

Research Update on Fish Oil Supplements

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Researchers performed a meta-analysis of studies that examined EPA and DHA as dietary supplements to see if there was a reduction in CVD events and mortality. In this study, researchers included 40 studies with 135,267 participants. While they examined many different variables, including whether EPA was better than DHA and whether they could find the best combination or ratio, almost every analysis they ran demonstrated benefits for those who use fish oil supplements: a 13% decrease in the risk of a heart attack, a 10% decrease in any coronary heart disease event, and a 35% reduction in the risk of a fatal heart attack.

For me, the most significant finding was that there was a dose-response effect of taking fish oil supplements. In other words, CVD events decreased with higher intake of fish oil supplements.

The Problems with the Prescription Study

There were three issues with the EVAPORATE study I talked about in Thursday’s Memo. First, there was a significant loss of subjects. Most of the loss was in the experimental group, which reduced the number of subjects from 40 to 31.

Second, they did not compare the prescription fish oil with an equivalent amount of fish oil dietary supplement, whether it contained DHA or not, which seems to be a glaring omission to me.

Finally, the study was funded by the manufacturer; several of the researchers had a relationship with the pharmaceutical manufacturer as well. That doesn’t mean anything shady was going on, but it does put in question the conclusions that can be drawn about the significance of the entire clinical trial.

The Problem with the Fish Oil Supplement Study

The primary problem with the fish oil supplement study is that it was a meta-analysis. Even though that method is becoming popular, and even though by all accounts the researchers tried their best in selecting the correct studies for inclusion, there’s always the specter that they may have left out some studies. To their credit, they re-ran the analysis without several of the clinical trials and did get slightly different findings. However, it did not change the outcomes related to heart attacks or coronary heart disease events.

The study was funded by Global Organization for EPA and DHA Omega-3s. Just as with the pharmaceutical study, there’s an inherent bias implied. In both cases though, if the funding organizations didn’t sponsor the research, who would? There are only so many research dollars available, and many dollars are being siphoned off to fund urgent COVID-19 studies.

The Bottom Line

I think that these studies establish that fish oil is beneficial to reduce CVD events and reduce disease progression. Because there appears to be a dose-response relationship to fish oil and the reduction of CVD risk, the higher amount of fish oil a person takes, up to four grams, the better the potential outcomes.

Which one is better: prescription versus supplements? Until there’s a study that directly compares prescription fish oil to fish oil supplements, I don’t believe it matters; both studies we reviewed demonstrate benefits. The key is that if you have been diagnosed with CVD, you should take fish oil. Talk it over with your physician first and then get going. Your heart will love you for it. And don’t forget to eat better and move more as well.

What are you prepared to do today?

        Dr. Chet

References:
1. European Heart Journal (2020) 00, 1–8 doi:10.1093/eurheartj/ehaa652
2. https://doi.org/10.1016/j.mayocp.2020.08.034

Research Update on Prescription Fish Oil

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Let’s begin by taking a look at the prescription fish oil supplement medication. To review, this is a 100%-EPA fish oil that received FDA approval in December of 2019. The amount prescribed for people with high triglycerides is four grams of highly processed fish oil per day. Data from the REDUCE-IT trial suggested that there was a 25% decrease in mortality in the experimental group compared with the control group.

The current trial was called the EVAPORATE trial: Effect of Vascepa on Improving Coronary Atherosclerosis in People with High Triglycerides Taking Statin Therapy. The study began with 80 men and women, ages 30-85, with greater than 20% blockage in at least one of their coronary arteries, elevated triglycerides, and taking statin therapy; 68 subjects completed the 18-month study. The primary endpoint was to see if there was any reduction in plaque buildup in the coronary arteries.

The subjects in the prescription fish oil group saw a 17% decrease in overall arterial plaque; there was a plaque increase in the placebo group. The researchers did not track cardiovascular events or mortality in this study. We’ll take a look at the OTC fish oil supplement study on Saturday as well as determine the clinical significance of each trial.

What are you prepared to do today?

        Dr. Chet

References:
1. European Heart Journal (2020) 00, 1–8 doi:10.1093/eurheartj/ehaa652
2. https://doi.org/10.1016/j.mayocp.2020.08.034

Research Update: Fish Oil and Heart Disease

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The prescription fish oil Vascepa has been approved since December of last year. The fish oil medication was originally intended for those who had a family history of high triglycerides of 500 mg/dl or greater. In the approval process, the recommendation was lowered to those whose triglycerides were at least 150 mg/dl and who were taking a statin medication. But the research hasn’t stopped.

Research on Vascepa as well as over-the-counter (OTC) fish oil supplements continues. From the pharmaceutical perspective, more research on the use of the medication could result in an increase in the potential applications of this pharmaceutical. From the dietary supplement perspective, research may help establish the efficacy of using fish oil dietary supplements instead of the prescription medication

Last week within one day of each other, studies on prescription fish oil and fish oil supplements were published that both demonstrated significant benefits. We’ll review those studies the rest of the week and see if we can find out whether fish oil dietary supplements match up with pharmaceutical fish oil. If you want a preview of the studies, check the references below; they’re both open access.

What are you prepared to do today?

        Dr. Chet

References:
1. European Heart Journal (2020) 00, 1–8 doi:10.1093/eurheartj/ehaa652
2. https://doi.org/10.1016/j.mayocp.2020.08.034

It’s Official: Prescription Fish Oil

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The U.S. Food and Drug Administration approved the prescription fish oil Vascepa for expanded use on Friday, December 13. The approval for the medication is for the secondary prevention of cardiovascular disease in patients under the following conditions:

  • Triglycerides above 150 mg/dl for everyone with diagnosed CVD and taking a statin medication.
  • Diabetes and two or more additional risk factors for CVD along with taking a statin medication.

The modifiable risk factors for CVD include smoking, obesity, high cholesterol, hypertension, and sedentary living. Remember from our prior series, secondary prevention may help reduce the risk of CVD symptoms developing.

My concerns are the same as they were before. Triglycerides less than 250 mg/dl can be resolved by diet and exercise in most people. Because the mechanism of action is unknown as to how the prescription works, there’s no reason to think that reducing triglycerides by lifestyle change won’t work as well as the prescription; the clinical trial didn’t track this data.

Speaking of lifestyle change, keep in mind the website specials on the Optimal Performance program as we get ready for the New Year. The Basic Meal Plan will teach you how to change your diet to reduce triglyceride levels if your levels are too high.

What are you prepared to do today?

        Dr. Chet

References:
1. http://bit.ly/36EbsYK
2. N Engl J Med 2019;380:11-22. DOI: 10.1056/NEJMoa1812792.

Prescription Fish Oil: Questions Remain

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The REDUCE-IT clinical trial formed the basis for the expanded recommendations for use of Vascepa, the prescription fish-oil medication. This was an expensive trial, involving 11 countries and hundreds of medical centers with 999 physicians who recruited subjects, collected data, and kept track of the subjects for close to five years. With over 8,000 subjects, this was no easy task. As I said in Thursday’s Memo, they examined the primary and secondary prevention when the medication is taken with statins versus a placebo with statins.

While this was a tremendous effort, there are still some concerns, in my opinion.

Study Concerns

A board made up of physicians and the pharmaceutical company’s staff designed the study and helped execute it; the pharmaceutical company paid for the clinical trial, collected and managed the data, analyzed the data, and interpreted the results. Then the statistics were reviewed by an independent statistician. This creates a huge conflict of interest regardless of safeguards that may have been put in place.

When any type of study is supported by companies with vested interests in the outcome, there will always be questions. That has been true for every dietary supplement manufacturer that’s ever funded a study as well as the milk and sugar industry. It’s especially true for this study. I began by talking about a report from the financial sector. Billions of dollars are on the line. That has to be considered by the FDA before final approval is given.

I have a tendency to have faith in science, as skeptical as I may be at times. And that’s where my concerns lie; not in the financial aspect but in the study design and results.

My Concerns

As complicated as this study was, it was incomplete in my opinion. They did not collect any data on the subjects’ diet; a small change in diet could have reduced triglycerides (TG) enough to have a positive impact on secondary outcomes. The median change in TG over five years with the medication was 45 mg/dl, from about 215 down to 170 in the medication group, while it was reduced 13 mg/dl in the placebo group. We don’t know whether a group that focused on dietary changes to reduce TG would have the same reduction in CVD events; that would have been an excellent addition to the study design.

They also didn’t have a group using fish oil from dietary supplements. True, it’s not their responsibility, but we can’t know whether the same benefit might not occur if the dosing of EPA were equal:

  • Almost every study that has used fish oil to examine whether CVD outcomes could be reduced has used fish oil with 1 gram of EPA.
  • If the amount of EPA were the same, a head-to-head comparison between a supplement and medication that each had 4 grams EPA might have found a similar benefit.

The real issue is that we don’t know what makes the fish-oil medication work, just like we don’t know completely how dietary omega-3 fatty acids work. Is it just the reduction in the TG or how the oils work in the body? Are genetics involved? Diet? The microbiome? We have no idea at this time.

The Bottom Line

I’ll keep on eye on the approval process for this fish-oil pharmaceutical and let you know how it will be prescribed in the future. The decrease in TG found in the study can be done with lifestyle changes alone, so is it going to be worth the cost of a pharmaceutical for a slight reduction in CVD events? Remember the difference between medication and placebo was just 4.8%. If you fall in that category, you’ll have to decide for yourself: pharmaceutical fish oil or lifestyle change. In this case, a little work may go a long way.

What are you prepared to do today?

        Dr. Chet

P.S. This will be the last Memo until after Thanksgiving. Paula and I are doing something we haven’t done in 20 years: go on a real vacation, just us, just for fun. No work of any type. Talk to you again December 3.

Reference: N Engl J Med 2019;380:11-22. DOI: 10.1056/NEJMoa1812792.

Primary vs. Secondary Meds

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One of the key questions for the FDA advisory panel to consider was whether the prescription fish oil was a primary preventer of cardiovascular disease or a secondary preventer. What’s the difference? Primary prevention of CVD would impact the disease and stop events before they occurred in the subjects taking the fish-oil medication. Secondary prevention would prevent additional CVD events from happening in those with established CVD.

If you were a type 2 diabetic with an additional risk for CVD such as obesity or being a smoker, taking the prescription fish oil with a statin would prevent a heart attack or stroke from happening; that’s primary prevention. Based on the Reduction of Cardiovascular Events with Icosa-pent Ethyl–Intervention Trial (REDUCE-IT) that didn’t happen, but it did prove to be a secondary preventer of additional cardiac events in those subjects in the study with established disease.

The question is whether the FDA will approve the prescription fish oil as a primary prevention or a secondary prevention pharmaceutical. The advisory panel seemed split on that count. The assumption by some was that there was disease present even though the event had yet to occur. Others said “prove it” by doing an actual clinical trial to examine that question. We’ll find out how the FDA decides later this year. As I mentioned yesterday, the financial implications are huge.

There are still some things to consider with the clinical trial, and I’ll cover that on Saturday.

What are you prepared to do today?

        Dr. Chet

Reference: N Engl J Med 2019;380:11-22. DOI: 10.1056/NEJMoa1812792.

Prescription Fish Oil Update

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“This Fish-Oil Heart Drug Could Be Big, Could Be Huge.” That was the headline in a well-known financial report after a Food and Drug Administration panel unanimously voted in favor of an expanded use for the prescription fish-oil drug. I mentioned this was a possibility when I first talked about Vascepa in October. The FDA is expected to make a final decision by the end of the year.

What is the expanded use? The medication could be prescribed to those who have established heart disease or type 2 diabetes with another CVD risk factor and are already taking statin medications to lower cholesterol. The advisory panel approved the use because research showed that when combined with statins, it could reduce CVD endpoints such as death, heart attacks, and strokes by an additional 4.8% when compared to a placebo over a 4.9 year follow-up period, 17.2% versus 22%.

One more thing. The medication could be prescribed to those with triglycerides as low as 150 mg/dl. That would include millions more potential users in the U.S. and Canada alone. You can see why the headline was in the financial news; the potential profit for investors could be huge. A lot is riding on what the FDA decides. I’ll explain that on Thursday.

What are you prepared to do today?

        Dr. Chet

Reference: Bloomberg Online. Max Nisen. Posted 11-15-2019.

Should You Try Prescription Fish Oil?

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The final marketing point that the prescription fish oil supplement makes is that the DHA omega-3 fatty acid found in many heart healthy fish oil blends may raise LDL-cholesterol. That’s the cholesterol, known as the lousy cholesterol, associated with an increased risk of cardiovascular disease.

Based on the studies I read, there may be a small increase in LDL-cholesterol in some studies. What they fail to mention is that there’s more than one type of LDL-cholesterol. The small, dense LDL cholesterol has been shown to be associated in CVD even when LDL-cholesterol is in the normal range; the large and fluffy LDL-cholesterol seems to have no relationship with CVD. The supplement fish oils that contain DHA seem to raise only the large LDL-cholesterol. That has led other researchers to call the effect of fish oil on LDL to be cardioprotective at best and benign at worst.

The Issues with the Marketing of Rx Fish Oil

Every company wants to put their best foot forward and prescription fish oil is no different. In reviewing the marketing materials as well as the research, here are my concerns:

  • The results of the studies they cite show a decrease in triglycerides of 33%. The mean level of triglycerides in one of the studies was about 660 mg/dl. That means it dropped the mean level to 440 mg/dl. While statistically significant, there’s no way to know whether that’s clinically significant in reducing the overall risk of CVD because the studies were so short.
  • The company clearly states that this medication is clinically relevant only to people with triglycerides greater 500 mg/dl; that’s a very small percentage of patients who may have familial high cholesterol. For the typical person with high triglycerides, this medication is not appropriate. That doesn’t mean it’s illegal to prescribe it for people with triglycerides between 250 and 500, but there’s also no evidence that it’s better than a change in diet or exercise. Will it be prescribed only for people with high triglycerides? We’ll see.
  • The company did not run comparative studies against fish oil supplements or with diet and exercise alone. Seems like that would be obvious.
  • Finally, while there are programs to get this medication for lower prices, I checked with my prescription plan and the cost would be $375 per month. For that kind of money, you can have someone prepare healthy meals specifically designed to reduce your triglycerides or take a class to learn to prepare them yourself; you could definitely join and inexpensive gym and buy more fresh fruits and vegetables.

The Bottom Line

Similar to statin medications when they were introduced decades ago, prescription fish oil should be limited to a very specific part of the population with familial high triglycerides. That’s all—no one else.

As for fish oil supplements, the issues they point out in their marketing material are not significant. You never use dietary supplements to treat any disease, but that doesn’t mean they can’t help you compensate for nutritional deficiencies. There will be a difference in the quality of any supplement so make sure you choose a quality manufacturer.

For the bulk of the population to reduce their triglycerides, reducing refined carbohydrates, saturated fats, and alcohol, increasing vegetable and fruit intake, and getting some exercise will help most. Like I always say: Eat better. Eat less. Move more.

What are you prepared to do today?

        Dr. Chet

References:
1. http://dx.doi.org/10.1016/j.atherosclerosis.2016.08.005.
2. J Clin Endocrinol Metab. 2018 Aug 1;103(8):2909-2917.
3. Am J Clin Nutr. 2004 Apr;79(4):558-63.

Fish Oil: Medication versus Supplements

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Before I address the concerns about fish oil supplements put forth by the Vascepa® prescription omega-3 website, it’s important to understand that all prescription and over-the-counter medications have been approved by the U.S. Food and Drug Administration (FDA). That means they have spent a significant amount of money—sometimes over $1 billion—to prove that the treatment claims are significant, and you can’t take that away from them. But marketing is a different story, so let’s look at what they say.

“Fish oil supplements are not FDA-approved.” True; no dietary supplement is FDA-approved, but that doesn’t mean they’re not regulated. They also can’t make claims about curing diseases.

“Daily dose could require 10 to 40 capsules to equal the prescription EPA omega-3.” That depends on the brand purchased, so that critique is weak.

“Fish oil supplements can leave a fish-y aftertaste.” Really? It’s fish oil, what would you expect? (Keeping the supplements in the refrigerator may help with that as well as taking fish oil before meals.) They suggest that the oils turn rancid and that causes the taste, but they offer no proof of that claim.

The last critique they make of fish oil supplements is that “Many contain another omega-3 fatty acid called DHA.” They say DHA can raise LDL cholesterol. I’ll address that claim and provide some concerns I have with the prescription omega-3 and how it’s being marketed on Saturday.

What are you prepared to do today?

        Dr. Chet

Treatment for High Triglycerides

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Hypertriglyceridemia, the medical term for high triglycerides, is a risk for cardiovascular disease. Recently I spotted a health headline from a medical newsletter that read “Omega-3 Fatty Acid Medications Can Boost Cardiovascular Health.” The word that caught my attention was “medications” so I checked it out.

The article described the benefits of recently approved medications based on marine omega-3 fatty acids. I checked out the latest one called Vascepa®. This is a purified form of fish oil that, according to the data on its website, can lower triglycerides up to 33%. Sounds impressive.

Back to the newsletter article: the author interviewed the lead author of a review paper that stated that prescription omega-3s are effective in lowering high triglycerides. Then she went on to say to avoid omega-3s from dietary supplements because they haven’t been proven to lower triglycerides as the prescription omega-3s have.

The website for Vascepa went a lot further in criticizing omega-3 supplements. What were their objections? Is a prescription the best way to go to treat hypertriglyceridemia? That’s what I’ll cover the rest of this week.

What are you prepared to do today?

        Dr. Chet

Reference: https://www.medicalnewstoday.com/articles/326146.php