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.
