Do Statins Really Work?

Author: Dr. Stephen Chaney

Statins – those ubiquitous drugs used to lower cholesterol levels – are big business!

Over 20 million Americans are currently being treated with statin drugs at a cost that runs into billions of dollars every year. And cardiologists have just recommended that another 20 million Americans consider using cholesterol lowering drugs. 44% of the men and 22% of the women in this country are now being told that they should be using statin drugs.

Some of my cardiologist friends are so convinced that statin drugs prevent death from heart attacks that they have said, only half-joking, that we should just add statins to the water supply.

Are Cholesterol-Lowering Drugs Right For You?

Is the faith of doctors in the power of statin drugs to prevent death from heart disease justified? To answer that question in full we need to look at people who have already survived a heart attack and people who have never had a heart attack separately.

If you’ve already had a heart attack the evidence is clear cut.

If you have had a heart attack, there is good evidence that statins will reduce your risk of dying from a second heart attack.

In the technical jargon of the scientific world that is referred to as secondary prevention.

But what about those millions of Americans who are being prescribed statin drugs who have never had a heart attack? This is something we scientists refer to as primary prevention.

What Do The Studies Actually Say About Statins And Primary Prevention?

Here the evidence is not clear at all. Two major reports have cast doubt on the assumption that statins actually do prevent heart attacks in people who have not already had a first heart attack.

In the first study, Dr. Kausik Ray and colleagues from Cambridge University in England performed a meta-analyis of 11 clinical studies involving over 65,000 participants (Ray et al, Arch. Int. Med., 170: 1024-1031, 2010). They focused on those participants in the studies who had not previously had a heart attack (primary prevention).

They found that the use of statins over an average of 3.7 years had no statistically significant effect on mortality. In short, statins had no effect on the risk of dying from heart disease or any other cause.

Dr. Sreenivasa Sechasai, one of the doctors involved in the study, said “We didn’t find a significant reduction in death despite having such a huge sample size. This is the totality of evidence in primary prevention. So if we can’t show a reduction with this data, it is unlikely to be there.”

The second study was a Cochrane Systemic Review of statins published January 19th, 2011. It stated that there was not enough scientific evidence to recommend the use of statins in people with no previous history of heart disease with some caveats (see below).

To help you understand the significance of that conclusion, let me give you a bit of background:

First you need to understand that the Cochrane Collaboration is an independent, non-profit organization that carefully reviews the scientific evidence behind medical treatments and proposed medical treatments.

Cochrane Reviews are considered the “Holy Grail” of evidence-based medicine (ie. medicine based on the best scientific evidence rather than what the pharmaceutical companies would have you believe).

So when a Cochrane Review concludes that there isn’t enough evidence to recommend use of statins in patients with no prior history of heart disease that is pretty big news in the medical world.

How Should These Studies Be Interpreted?

Please don’t misinterpret what I am saying. The Cochrane Review said that statin drugs are overprescribed, but it did not say that everyone who has not had a heart attack will not benefit from statins. It said that there are a number of risk factors that need to be considered in evaluating individual patients for statin use.

Simply put, that means that it is not as simple as saying that everyone with no previous history of heart disease should not be on statin drugs.

If you are currently taking statin drugs and you have no previous history of heart disease, you may want to discuss with your physician whether the Cochrane Review of statin drugs changes their opinion of whether se of those drugs is still warranted for you.

But the bottom line is that only your physician is trained to take into account all of the factors that increase your risk of heart disease and the best therapeutic approach for reducing your risk of heart attack.

There Is A Double Standard In The Medical Community

More importantly, these studies highlight the difficulty in showing that anything works when you start out with a healthy group of adults with no prior evidence of disease (primary prevention).

And, the way that doctors have responded to primary prevention studies shows that there is a double standard in how primary prevention trials are interpreted in the medical community. For example:

There is no good evidence that statins prevent fatal heart attacks in healthy people.

However, because statins do work in high risk patients, most doctors recommend their use by millions of Americans who have never had a heart attack.

There is also no good evidence that nutrients like vitamin E and omega-3 fatty acids prevent fatal heart attacks in healthy people.

However, there is evidence that both vitamin E and omega-3 fatty acids prevent heart attacks in high risk patients, yet most doctors will tell you they are a waste of money.

It is food for thought.

The Bottom Line

1) Statin drugs clearly save lives when used by people who have already had a heart attack.

2) On the other hand, there is no proof that statin drugs prevent heart attacks in people who have not previously had a heart attack

3) Statin drugs do have side effects. Increased risk of diabetes, liver damage, muscle damage and kidney failure are the best documented, although memory loss has also been reported.

4) I am not recommending that you stop using statin drugs without consulting your doctor. I am suggesting that you discuss the benefits and risks of statin drug use with your doctor.

5) Perhaps the most important poin tto come out of these studies is that it almost impossible to prove the benefit of any intervention in a primary prevention trial. If you can’t prove that statins work in healthy people, it is not surprising that it is difficult to prove that other interventions work.

6) Finally, the way that these studies have been interpreted shows that there is a clear double standard in how the medical community evaluates primary intervention trials.

Statin drugs don’t show any benefit in a primary prevention setting, yet most doctors still recommend them.

Vitamin E and omega-3 fatty acids don’t show any benefit in a primary prevention setting, and most doctors recommend against them.

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

The Fine Print Behind The Misleading Headline

Author: Dr. Stephen Chaney

I hadn’t paid much attention to the headlines saying “Statin Use May Decrease Parkinson’s Risk” until the other day when I happened to glance a couple of lines below the headline and spotted a statement saying “Study Shows That Discontinuation of Statin Therapy Increases Risk of Parkinson’s”.

I immediately said to myself “That’s bizarre. There is a total disconnect between the headlines and the study.” If you really wanted to determine whether statin use reduced the risk of Parkinson’s, you would compare the incidence of Parkinson’s disease in a group of statin users and a matched group who did not use statins.

It turns out those studies have been done, and they were inconclusive – some studies showed a slight increase in Parkinson’s in statin users, some showed a slight decrease, and most showed no correlation between statin use and Parkinson’s.

In that context, this study could equally well have been interpreted as suggesting that statin use increased the risk of Parkinson’s, but somehow none of the headlines mentioned that possibility.

Are Both Possibilities Plausible?

Let’s look at each possibility in detail. The reasoning is complex, but let me try to walk you through it.

Could Statins Decrease The Risk Of Parkinson’s

Parkinson’s is caused by the progressive degeneration of the brain neurons that produce a chemical messenger called dopamine that controls muscle movement. However, the causes of nerve degeneration in Parkinson’s patients are largely unknown.

Genetics may play a small role. Environmental toxins may play a role. But most experts feel that Parkinson’s patients produce an excess of free radicals, and it is the oxidative damage caused by those free radicals that results in the loss of the ability of neurons to produce dopamine.

But even that is not the whole answer. The brain is normally able to use coenzyme Q10, which is very abundant in brain, and other antioxidants to destroy free radicals before they damage brain neurons. Somehow in Parkinson’s patients free radical production and antioxidant production have gotten out of balance.

Advocates of the theory that statins may decrease the risk of Parkinson’s, point out that statins decrease oxidative damage. So if a person was predisposed to developing Parkinson’s and oxidative damage is a major cause of Parkinson’s, it is theoretically possible that statins could slow the progression to Parkinson’s while they were taking the drug. Of course, once they stopped taking the drug the oxidative damage to dopamine-producing neurons would resume and Parkinson’s would eventually develop.

In this model- Let’s call it Model A:

1) Oxidative damage of dopamine-producing neurons was caused by some unspecified external agent.

2) Statins protected the neurons from oxidative damage while they were being used.

3) Once the statin drugs were discontinued oxidative damage resumed and the risk of developing Parkinson’s increased.

This is the model favored by the authors and repeated in all of the headlines you saw.

Could Statins Increase The Risk Of Parkinson’s?

Statins also interfere with the synthesis of cholesterol and coenzyme Q10, and these are both absolutely essential for brain function. Let’s start with cholesterol:

20% of the body’s membrane cholesterol is found in the myelin sheath that coats the brain’s neurons (You can think of the myelin sheath as analogous to the plastic coating that insulates an electrical wire).

Cholesterol can’t cross the blood-brain barrier, which means that the brain cannot utilize cholesterol from the bloodstream . It has to make its own cholesterol.

As for coenzyme Q10:

It is not only a powerful antioxidant. It is also absolutely essential for cellular energy production.

The brain has tremendous energy requirements. The brain accounts for 20% of the energy utilization of our body. Neurons burn 2 times more energy than other cells in our body.

For both of these reasons, many experts have cautioned that statin drugs have the potential to cause neurodegenerative diseases such as Parkinson’s. In this model – Lets call it model B:

1) The statin drugs themselves are damaging the dopamine-producing neurons by inhibiting cholesterol and coenzyme Q10 synthesis in the brain.

2) The antioxidant effects of the statin drugs were masking the damage caused by the statins while the drugs were being used.

3) Once the statin drugs were discontinued the underlying damage was unmasked and the patients quickly developed Parkinson’s.

What Did The Study Actually Show?

The study (Lee et al, Neurology, 81: 410-416, 2013) looked at 43,810 statin users on the island of Taiwan. The Taiwanese Health System keeps extensive records of prescription use and health conditions of everyone on the island. It also requires that statin use be discontinued as soon as the patient reach their target of < 100 mg/dL LDL cholesterol, so they had the perfect population base to study what happens when you discontinue statin therapy.

The results were:

The patients who discontinued statin therapy were 42% less likely to develop Parkinson’s that those who continued on statin therapy. That result is consistent with both models A & B.

The increased risk of developing Parkinson’s when the drug was discontinued was only seen for the statin drugs like simvastatin and atorvastatin that are able to cross the blood brain barrier. That result is actually a bit more consistent with model B (Remember that the brain has to be able to make its own cholesterol and statins block cholesterol production).

When the study compared people using statin drugs to those not using statin drugs there was no significant difference in the prevalence of Parkinson’s – even for those statin drugs that cross the blood brain barrier. That means that merely being on a statin drug did not influence the risk of developing Parkinson’s. It was only when patients were on statin drugs for a period of time and were subsequently taken off statins that the risk of developing Parkinson’s was affected – and the effect was to increase risk! In the context of the first two findings, that result is also a bit more consistent with model B.

The Bottom Line:

If I were writing one of those medical blogs, I would have probably have gone with the party line and told you that statins decrease your risk of developing Parkinson’s. And if I were one of those health bloggers who never let the facts get in the way of a good story, I’d probably be scaring you with headlines saying that statins increase your risk of Parkinson’s.

But, I’m a scientist. I actually read the article, and I tell it to you like it is. Here’s your bottom line.

1) Ignore the headlines. The study they are talking about can’t distinguish between statins increasing or decreasing the risk of Parkinson’s. Don’t let anyone tell you that reducing the risk of Parkinson’s is a side benefit of statin therapy. That simply has not been proven.

2) The study does clearly show that discontinuing the statin drugs simvastatin and atorvastatin is associated with increased risk of developing Parkinson’s. That’s a big red flag for me, because 53% of patients discontinue statin therapy because of side effects, cost or other reasons.

3) However, statin drugs do save lives, especially for people who have already had a heart attack, so talk with your doctor about the benefits and risks of statin drugs, and which statin drugs are best for you.