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We've been told that medications to lower cholesterol will save lives.
We repeatedly hear from patients that their doctors tell them, 'If you don't take this,
you will die.'
Over 40 million people worldwide take drugs to lower their cholesterol. But now there's
evidence that the majority of them won't benefit.
None of those people are less likely to die.
I speak to doctors accusing the drug companies of distorting the evidence about the drug's
side effects.
Of course they're going to try to minimise the adverse events 'cause that will increase
the sales of their drugs.
In its effect it's certainly scientific fraud, and in its effect it's organised crime.
So how do these drugs work? And are they really safe? I've come to the United States to investigate
how drugs to lower cholesterol came to be the most widely prescribed drugs in the history
of medicine.
The '80s saw the debut of a new weapon in the battle against heart disease - a novel
class of drugs called 'statins' that lowered cholesterol like no other medication before
them.
They were heralded as... Nirvana. The next great thing. Because all of a sudden, now
you're getting 30-40% reduction with statins, which was huge. And this was great news to
the people who were pushing the cholesterol theory, because they said, 'Aha! Now we don't
have to settle for these piddling little amounts anymore - we can really show how important
cholesterol is by knocking it way down.'
..medical information comes along that say you may need to get...
In the US, influential TV ads like this use popular actors to boast the enormous potential
of these drugs.
Crestor, along with diet, can lower bad cholesterol by up to 52%.
But the reality is - lowering your cholesterol with medication doesn't guarantee you won't
have a heart attack.
The marketing concentrates on the fact that you can lower your cholesterol as if that
was the end in itself, which it is not. Cholesterol's just a lab number. Who cares about lowering
cholesterol unless it actually translates into a benefit to patients?
Over the decades, drug companies have had an enormous vested interest in statin drugs.
It's the most profitable group of drugs in the history of the world. Something like $15
to 25 billion, with a 'B', per year, spent on these drugs. So that's higher than the
gross national product of many countries around the world.
Lipitor is the bestselling drug in history. So in terms of cost, total sales of Lipitor
have been in the range of $140 billion since it came on the market in 1996.
Statins work by disabling a critical step early in the formation of cholesterol.
There's a pathway that produces cholesterol in the body. You could think of it like a
tree. So, we've decided collectively that one of the branches of this tree is bad, meaning
cholesterol. So we've decided that the best way to get rid of that branch is to cut the
tree off at the root.
Statins inhibit this enzyme, which is also required for essential molecules like Coenzyme
Q10. Nutritionist Dr Jonny Bowden says CoQ10 is essential for optimal heart muscle function.
This is partly, we believe, why so many side effects have to do with lack of energy, muscle
pain - because Coenzyme Q10 is so vital. So what's the irony of giving people a drug to
reduce something that probably doesn't even have that much to do with heart disease, that
also reduces one of the molecules that's most necessary for heart health? How insane is
that?
It's assumed that the cholesterols a toxic substance in your body and getting it as low
as you can is a good thing. Well, cholesterol is the organic molecule that's most common
in your brain, by weight. It's in every cell wall. It's the precursor of many of the hormones
in our body. It's an enormously complex molecule. And to think that you can radically pull this
out of the body and not have consequences is just... it's ridiculous, it's such bad
science.
It's been about 30 years since statins were first introduced as the new blockbuster drug
in heart disease. And millions of people around the world are being prescribed these medications.
But many are concerned that the benefits of these drugs have been grossly exaggerated.
Professor Rita Redberg is a world-renowned cardiologist. She says, barring a genetic
condition, the only people who live longer by taking a statin are those that have already
had a heart attack or stroke.
Valve's working great.
That's good.
Yeah.
And of them, only a very small number will benefit.
One or two people in a hundred will benefit from taking a statin. What people don't understand
is that means the other 98 will get no benefit at all. It's not going to reduce their chance
of dying.
But this hasn't limited their use. These drugs are now being widely prescribed to relatively
healthy people - those without diagnosed heart disease. And Dr Redberg warns most of them
won't benefit.
For healthy people, even people that have a lot of risk factors. So they might have
high blood pressure, they might smoke, they might have diabetes. The data is not there
to suggest that those people are better off taking a statin. No, I don't think it's a
wonder drug.
But Dr David Sullivan disagrees. He says all the risk factors should be considered equally,
including cholesterol.
If you want to mount these arguments about not treating the cholesterol, you've got to
take the responsibility of saying it's not necessary to treat these other risk factors
either. I would certainly encourage people who are considering cessation of treatment
for perceived side effects and so forth to discuss it with their doctor.
In 2012 there was an interesting turn of events. The CTT collaboration, a highly regarded group
of researchers, reanalysed all of the old data with different methods and concluded
that statins were effective for the wider population. The report was subject to harsh
criticism, but it's still the data that many cardiologists turn to. The media jumped on
board and reported that everyone over the age of 50 should be taking a statin to reduce
their risk of heart disease, even if you had normal cholesterol. But Professor Redberg
says there's a downside.
None of those people are less likely to die. So you can take a statin for many, many years
and you're just as likely to die as if you had not taken a statin.
Unless you've already been diagnosed with heart disease, then taking a statin won't
help you live longer. It may reduce your risk of a cardiovascular event, but it may also
increase your risk of developing something else, like diabetes. Either way, taking a
statin won't extend your life span.
Dr Abramson says cardiologists are so focused on how these drugs prevent blood vessel disease
they often overlook the other problems caused by statins.
People are more than their cardiovascular system, and what we really want to do is improve
people's overall health, longevity and the risk of serious illness. If you look at overall
health, we haven't done anything for them. Now, do people want to take a statin to trade
one cardiovascular event for some other very serious illness - in other words, no net benefit
- and expose themself to the risk of harm from the statins? Do you want to do that?
I think it's a bad deal. If somebody has a particular fear of heart disease and says,
'Look, I don't care if I get diabetes, I don't care if I have muscle symptoms, I don't care
if I can't exercise the way I want to exercise, I do not want to have heart disease,' fine,
take a statin. But understand that that's why you're taking a statin, not because it's
going to improve your overall health.
Cardiologist Dr Ernest Curtis says the absolute benefit of statins is so minor that it's unlikely
to be because of their ability to lower cholesterol. He says statins probably work through other
mechanisms.
It seems very likely that the amount of reduction that they saw with the statin agents could
easily be due to its effect on the blood clotting, and possibly the anti-inflammatory effect,
and have nothing to do with the cholesterol.
Dr Golomb has scrutinised the data, and she's even more sceptical about the value of these
drugs, especially in women.
Right now the evidence has not supported benefit to women, even if they have heart disease,
in terms of mortality and all cause morbidity. It has not shown benefit to elderly, even
if they have heart disease. In fact, in the 4S trial, there was a 12% increase in mortality
in the women in that group who were assigned to statin rather than placebo. So the evidence
really doesn't support that the benefit is the same for women and for men. And on top
of that, women are at higher risk of complications from statins.
Should women take cholesterol-lowering medication?
In general, no. Now there may be exceptions. Medicine actually does have an element of
art. And if women are from a family with severe familial hyperlipidaemia, where a lot of people
are dying from heart disease in their 30s and 40s, that's a group where I would say
there is an art.
There are now calls for patients to give written consent before taking a statin.
If you do plan to give statins to women, to elderly, to people at low risk, they should
sign a consent form saying they understand that they're receiving a drug that will not
extend their life, but will only shift the cause of death. I think patients have a right
to know that before they agree to take on a medication.
The National Heart Foundation of Australia agrees that people are being prescribed statins
unnecessarily.
I would agree that there are people in Australia today who are being treated for cholesterol
where their cardiovascular risk is not high. And you have to question whether they should
in fact actually be on that.
A report estimated around 75% of people taking statins are in the low to moderate risk category,
and, according to these researchers, that means up to 30 million people are taking a
drug that won't offer them the benefit of living any longer.
My doctor pointed out that my cholesterol levels were high and that I should take some
sort of medication to reduce the cholesterol level.
There was nothing wrong with Edward's health, apart from his high cholesterol. He took his
doctor's advice and began taking a statin.
After about two weeks I was having a difficult time walking in the daytime, and at night
I had trouble sleeping, my legs ached. I was definitely experiencing a memory loss. I didn't
feel that I could recall things as clearly as I did before I was taking the statin.
Statins have a long list of side effects - like muscle weakness, memory loss, and, in rare
cases, a potentially fatal condition called rhabdomyolysis, where muscles break down and
cause kidney failure. Edward decided to stop taking his medication.
I started feeling better after about three weeks to maybe a month afterwards.
How long did it take for you to get 100% improvement?
100% better took from the time I stopped taking the statins, it took six months.
They feel like they're in a fog, they can't get out of their chair - side effects that
go away when they stop their statins. And I have patients come in and tell me they'd
rather be dead than keep taking the statin.
Some of them tell us that their doctors fire them as patients if they discontinue their
statins, which I really wonder about the ethics of. Some of the people that we hear from also
say that their doctor didn't believe them, that their problem couldn't be due to statins,
and based on how patients perceive it, badger or bully them into resuming or continuing
the medication. That's not an acceptable way for medicine, as a system, to be run.
But Dr Sullivan says it's possible that patients talk themselves into having side effects.
In alerting patients to some undesirable possibilities, and, in fact, maybe even through the power
of suggestion, lead them to believe that they're experiencing those particular issues, which
they would then blame on the drug when in fact it might be arising from other factors.
Their imagination?
Um, look, I'd be reluctant to... I think a lot of these things aren't imagined. I think
there are days when you can feel more of a muscle ache than others, and it can be age,
it can be all sorts of other things.
Dr Golomb makes a stunning accusation about why she believes some doctors in the US may
push their patients to take statins.
I think they often intentionally hide those risks because there are often physician incentives
that benefit the physician for having more patients on statins. So it pits physician
self-interest against patient benefit. This particular woman contacted me, and she had
left the practice that she was at because they insisted that at least... I believe it
was 80% of her patients be on statins. This has actually been written up in media as something
that is actually considered legal and acceptable. I can't see any way in which that's acceptable.
I'm literally the only researcher I know who studies this class of drugs who has a policy
not to take money from industry.
Statins are meant to be lifelong medications, but Dr Curtis says we don't know about the
long-term side effects.
The studies that have been done have generally been just a few years in duration. The long-term
effects may not show up for many years. It may take many years for a cancer that develops
to make itself manifest. Because cholesterol is so important in the brain, could it contribute
to dementia when someone gets older if you lower their cholesterol? We don't know. Again,
how would we be able to tie that to the drug? So all of these concerns about the unknown
long-term side effects are very serious, in my opinion.
Harvard Doctor John Abramson is an expert in litigation involving drug companies. He
says we're not being told the whole truth about the dangers of these drugs.
We're told over and over again that statins are extremely safe. And when you look at the
results of the clinical trials, you would conclude that they are safe. Problem is that
the clinical trials are not designed to pick up all the side effects.
The CTT collaboration, for example, use mostly drug company data, and report very low levels
of muscle side effects from statins. But when you look at the side effects in the general
population, it's 100 times higher.
Are the trials lying? No. I just don't think they ask the right questions. Why don't they
ask the right questions? It's not in the interest of the drug companies to ask the right questions.
So, it's creating the impression that the drugs are safe.
Another complication with clinical trials is that drug companies don't recruit volunteers
that reflect the typical patient on statins.
The problem with the study design is that we exclude people with chronic disease or
other comorbidities. We exclude people who are very old or very young, and we'll certainly
exclude people with other types of risk factors or diseases that may interfere with the metabolism
of the drug. So we often get a skewed picture of what the side effect profile is.
The fraction of people with problems in my sort of real-world, on-multiple-medications,
etc clinic is far higher. And I would say that in that sample it really seems in the
order of a third of patients that develop problems.
There are a lot of ways that one can manipulate data in a trial. Trials do what they call
a washout period, and what that means is before they choose the people that are going to be
in the trial, they give everybody the drug, and the people that have side effects get
excluded from the trial. And they say that so people aren't uncomfortable when they are
in the trial. But of course it takes out all the people that have side effects, and that's
very commonly done in drug trials.
So the side effects would be grossly underestimated.
Yes, it would definitely grossly underestimate the number of people that have side effects.
They're not as safe as they're made out to be, no.
In its effect, it's certainly scientific fraud, and in its effect it's organised crime. It's
always difficult to allege intent, but it is clear that manipulation of evidence subjects
many people to treatments that those people should never have been subjected to.
I think there is criminal activity that goes on. And I think when drug companies act in
ways that misrepresent information that leads to harm, they ought to be held responsible,
just like any other individual or organisation that conducts itself in a way that leads to
harming other people.
Drug companies have a history of illegal activity. This is just a sample of the billions of dollars
in fines they incur for things like fraud and bribery in any given year. In the '80s,
when President Reagan came into office and slashed funding to the national institutes
of health, it left a gaping hole for private industry to move in. Nowadays, around 85%
of trials are funded by drug companies. A review concluded that if a drug company paid
for a trial, it was 24% more likely to report the drug was effective and 87% less likely
to report the drug's side effects.
There is a sense that science is science, so it doesn't matter who pays for it. And
yet because the research is privatised, the fundamental purpose for which it's conducted
has changed. It's not to improve the public's health - it's to fulfil the fiduciary obligations
of the sponsors and create an opportunity to maximise profits instead of improve the
public's health.
Some might say that that's a rather cynical view of how science works.
To say it's cynical that commercial sponsorship of science taints the science is just totally
naive. It's silly. Business is in business. Their job is to make money. We ought to be
clear in our public discourse that to say we've got a bias in commercially sponsored
research is neither cynical, nor paranoid, nor impolite - it's a fact. So let's just
accept it as a fact and stop being naive at our own expense.
But, if big pharma doesn't pay, it will have to be the taxpayer.
A drug now costs about $2 billion to develop. The success rate of drugs is very low. You
know, is the public purse going to be willing to shell out, in advance, $2 billion for a
drug which it doesn't know the likely outcome of?
Arguably, the biggest ethical issue in science is that drug companies withhold unflattering
results. So, in the end, what we're presented with is a distortion of the data.
Two of the three major drug companies declined to comment. AstraZeneca denied these allegations,
stating that all their trials are publicly available. But in 2010, the drug-maker reportedly
paid a half a billion dollars to settle a class action after being accused of burying
information about the increased risk of diabetes seen with their widely prescribed anti-psychotic
drug, Seroquel.
I spend a lot of time as an expert in pharmaceutical litigation, and one thing you learn is that
you can't possibly know what's going with that drug unless you have access to the corporate
hard drives. If you want to know the truth about a drug, you need to have subpoena power
or, in litigation, discovery that gets you into those corporate hard drives. Because
without getting into the corporate hard drives, it's impossible to know what the real benefits
and the real risks of those drugs are.
Even the definition of 'high cholesterol' keeps changing. In 2004, a US panel of experts
decided to lower the threshold of cholesterol, which sparked outrage amongst many doctors.
More and more people think they have high cholesterol even though they don't have high
cholesterol.
By changing the definition, it meant that millions more people became eligible for statins,
and these thresholds were adopted by many countries around the world.
Has this been on the basis of any scientific data? Absolutely not. Absolutely not, no evidence
whatsoever, just the theory that less is better. You're creating more patients, you're creating
more people who now have something to worry about where they didn't have anything before.
But Dr Sullivan insists this was a good decision.
I think what we actually started off with was maybe appropriately conservative targets
which were really not in the patients' best interest. So the likely outcome is a further
reduction in targets.
More cholesterol lowering.
Yep, I think that's absolutely to be expected.
The decision to lower the threshold of cholesterol was a controversial one. An investigation
into the matter revealed eight out of nine panel members had a direct conflict of interest
after declaring financial ties to the companies that manufactured statins.
We don't have independent reviewers evaluating the data and making independent recommendations.
You might ask, 'Am I accusing these people of selling their opinion because they're getting
paid by the drug companies?' No, I'm not. I'm not accusing anybody of bad faith. But
the people the drug companies choose to pay are people who advocate the use of their drugs,
and have standing and presence and reputation that will enhance the sales of their drugs.
So do drug companies seek out doctors to be their mouthpieces?
Drug companies clearly seek out what's called key opinion leaders. These are people with
a national reputation who can create the street knowledge for practising physicians, that
this is the way things should be done.
There is ample published literature showing that doctors who receive money from drug companies
have more favourable attitudes and prescribing habits towards that drug.
There's no question that doctors are influenced by drug companies. And I hate to say it, but
drug reps showing up in nice suits and fancy women's clothes without much medical education
play a significant role in what doctors think. Now, there's no reason for doctors to be getting
their information from drug reps, my goodness. The drug rep's job is to increase the sales
of the drugs they represent. Doctors need to take some responsibility. They need to
do their best to get independent knowledge, and they need to put political pressure on
their governments to get the clinical trial data unsealed so they can know what the clinical
trials really showed.
Many doctors feel obliged to follow the guidelines, even if they don't agree with them.
They have to worry about malpractice suits if they don't follow the guidelines. An opposing
attorney could make them look very bad in court by saying, 'Well, doctor, do you think
you're smarter than this national group of recognised experts?' And this is a factor
that's impelling doctors to follow the guidelines.
The push to lower cholesterol in the wider population continues.
A group of doctors published an article claiming that statins could counter the effects of
eating a burger. They suggested that statins be handed out as free condiments, just like
ketchup.
Because it gives people that false reassurance that it's OK if you eat this food that is
not good for your health, because then you're going to take this pill that is going to make
it OK. And that's very attractive, but it is a fallacy, it's just not true. And it's
still bad for your health to eat processed foods, eat trans fats and have a regular diet
of fast food hamburgers.
And the absurdity doesn't stop there. Here in the US, it was even suggested that statins
be put in the public water supply.
I think this idea of handing out statins willy-nilly to everybody is totally irresponsible. You're
talking about a drug with potentially toxic side effects, and a drug whose quote ‘beneficial
effect' is extremely small, and whose benefit can be achieved with much less toxic drugs
and even with some non-drug treatments.
We're missing the message: that health rarely comes out of a bottle. Exercise and a Mediterranean-style
diet is the best way to prevent heart disease. I think virtually everybody agrees with that.
Now, it's very clear that when you look at the effects of exercise, they're far more
powerful than statins. Moderate exercise, exercising the equivalent of two hours of
brisk walking a week, adds about two years to your life compared to not exercising that
much. Two years. Now, for statins for low-risk people? No benefit in longevity. So do you
want to exercise, which is going to add two years to your life? Or do you want to take
a pill that's not going to lengthen your life and has the risk of side effects? It's craziness.
Until the science of clinical trials can break free from commercial interest, then decisions
about our health rest in the hands of big business.