Billions wasted on cholesterol myth

DRUG BUST
by Alan Cassels

The alleged benefits of lowering our cholesterol have never materialized and we have wasted tens of billions of dollars over the last two decades, deluded by a myth. It’s time to drop that myth.

Though it may appear to my readers that I have cried wolf far too often on cholesterol-lowering drugs, I’m prepared to howl at the moon at least one more time. If you’ve read my columns over the last decade, you’ve seen me rant about the futility and absolute waste involved in our society’s collective obsession with cholesterol and our foolishness in swallowing a paradigm promoted by the pharmaceutical industry and the specialists in their employ. The alleged benefits of lowering our cholesterol have never materialized and we have wasted tens of billions of dollars over the last two decades, deluded by a myth. It’s time to drop that myth.

Ever since the early 1990s when the first cholesterol lowering drugs were being introduced to the market, no one had really ever heard of “high cholesterol” and certainly no one was going to their doctor just to get something checked that they never knew existed, that they couldn’t feel and which was responsible for zero symptoms. Then along came the blockbuster statins and physicians followed guidelines that told them a patient’s cholesterol level was an important risk factor for death by coronary heart disease (CHD). The hypothesis said that if you measured and lowered the cholesterol of patients deemed “high risk,” those patients would live longer and avoid dying from heart attacks. So how’s that working out?

Not so well, according to a study published in March of this year that probably delivered some of the boldest evidence yet and which should absolutely trash our enthusiasm for lowering our cholesterol. A European research team led by Dr. Federico Vancheri of Italy looked at statin consumption across 12 countries in western Europe between the years 2000 and 2012. During that time, the use of statins increased dramatically all across Europe – as well as in North America – yet his team wanted to know how this increase was reflected in the numbers of people who died of heart attacks. After all, with statins being used by tens of millions of patients, how many fewer heart attack deaths were there?

Here’s the good news: in all countries over that 12 year period, there was lower CHD mortality in 2012 compared to 2000; that is to say, fewer deaths by heart attack. The drop in those numbers is thought to be attributed to a range of things: healthier diets, more exercise, lower rates of smoking, better treatment once you had established heart disease, and so on.

However, things didn’t look so good when you looked at individual countries. The researchers found that “when the different countries were compared, there was no evidence that higher statin utilization was associated with lower CHD mortality, nor was there evidence that a high increase in statin utilization between 2000 and 2012 was related to a larger reduction in CHD mortality.” In other words, despite all the statin prescribing, it had no effect on the one thing we expected to see: lower rates of heart attacks. This kind of research is not exactly new. There was an earlier Swedish study that showed the differences in a large sample of municipalities where the amount of statin prescribing had zero effect on the rate of heart attacks or CHD death.

Despite this kind of bad news for the statin manufacturers, the world is not exactly mourning the loss of a very costly – and now proven wastefully ineffective – pill. Just last month, many of us watched in horror as we witnessed a high-quality source of health information – the US Preventive Services Task Force (USPSTF) – come out with the astonishing recommendation that statins should be used by even more of us.

In their analysis, the USPSTF amassed a massive amount of data from over 70,000 patients from 19 different trials. They wrote that low-to-moderate-dose statins should be given to “adults aged 40 to 75 years without a history of cardiovascular disease (CVD), who have one or more CVD risk factors and a calculated 10-year CVD event risk of 10% or greater.” Practically speaking, this means tens of millions more Americans were offered statins.

Sounds good, right? Not so fast. Remember, the people they are recommending take statins are basically healthy, middle-aged people, folks with no established heart disease, 90% of whom will live perfectly happily without a heart attack or stroke over the next 10 years. These are NOT sick people perched on death’s doorstep.

So, what’s up? It always surprises me when an otherwise reputable and trustworthy source gives absurd advice, especially given all the statin scandals and shenanigans we’ve seen over the last two decades.

In case you don’t believe me, here are some key reasons we should ignore the advice to give more statins to more people, as the task force recommended. I must acknowledge Drs. Rita Redberg and Mitchell Katz who wrote a scintillating editorial on this USPSTF recommendation and whose arguments I am partially summarizing here.

The first thing to know is that the body of studies examined by the USPSTF is tainted, as it included many people taking statins for ‘secondary’ prevention – for example, people with established heart disease and hence considered at much higher risk. You cannot extrapolate how they fared on statins to healthier people without established heart disease.

The second thing is that the evidence they looked at didn’t contain the kind of detail we need. The USPSTF didn’t examine what we call primary data, which are the actual reports from the subjects in the statin trials. Without actual patient reports, we’re only getting the results of what someone has chosen to summarize for us. Sorry, that isn’t good enough. Also, if you only examined the published reports of statins, you are being naive because we know that most of the trials on statins were done by the manufacturers and they have a tendency to bury negative data. The result? An overly rosy picture of the effects of statins.

Thirdly, there was a major bit of missing information in those data, specifically what we call “all-cause mortality.” Only half of the trials they looked at reported how many patients died from cardiovascular causes, heart attacks and strokes. The problem with missing data is you are only getting half the picture so you end up concluding the drugs are safer than they actually are. You wouldn’t conclude how rich you are by only looking at your assets, would you? No, of course not. You need to know your liabilities and debts as well. Same with statins. Without both sides of the equation, you are at risk of being misled.

We need to remind ourselves of one key thing: people of ‘low risk’ may have very little chance of benefiting from a statin, but will have an equal chance of harm. In this group of healthy, low-risk people recommended to take statins, the benefit/harm math shifts and they are more likely to be hurt than helped.

Overall, the danger of recommendations like these is that more people will be convinced they are at high risk when they aren’t and take a drug that is unlikely to help because it is only proven to help those with established heart disease. We have known for a long time that statins can cause muscle aches, weakness, fatigue, cognitive dysfunction and an increased risk of diabetes. Why would you want to take your chances?

Maybe all the statin denialism is just part of the post-truth world and people tend to believe what they want to believe despite the overwhelming evidence in the other direction. Are you a ‘low-risk’ person who still wants to take a statin? Then you should have to pay for your denialism.

Statins are currently the fourth most costly drug to BC’s Pharmacare budget, and with over 400,000 British Columbians consuming statins every day, costing taxpayers and patients about $100 million per year, couldn’t we just admit the experiment is over, it was a failure and it’s time to move on?

Alan Cassels is a drug policy researcher and writer. In each of his past four books, the latest which is called The Cochrane Collaboration: Medicine’s Best Kept Secret, he has written about statins. Follow him on twitter @AkeCassels www.alancassels.com

Saying “know” – A 5-point primer on cholesterol-lowering drugs

 

DRUG BUST by Alan Cassels

I’ve got an idea. I think we should make t-shirts that say: He who dies with the lowest LDL doesn’t win. 
– John Abramson, author of Overdo$ed America

In my field, I see a lot of things that don’t connect. There’s the often uncomfortable, big disconnect between the data from a clinical study and the advertising and marketing that flows from it. Then there’s the disconnect between the meta-analysis of clinical trials of a particular class of drugs (an overview of all relevant studies) and the prescribing guidelines made for our physicians. And there’s the disconnect between the testimonials of experts who advise doctors on the safety of drugs and the self-reported experiences of real patients whose own horror stories of adverse drug effects don’t jibe with the picture painted for their doctors. In prescribing, there are disconnects everywhere.

You won’t find any bigger disconnects than the ones orbiting the cholesterol hypothesis where plenty of ignorance and self-delusion drives a lot of pharmaceutical consumption. This hypothesis, simply put, claims if your blood contains “high levels” of LDL or the “bad” type of cholesterol and low levels of the “good” type, HDL, you need to do whatever you can – alter your diet and start taking statins (cholesterol-lowering drugs) – to bring down the bad and bring up the good. LDL is believed to be more important so the lower the LDL, the better goes the hypothesis. Enter the drug industry.

Since cholesterol-lowering drugs (called statins because their names end in ‘statin’) are taken by almost everyone on the planet – young, old, healthy, sick and so on – they are the biggest blockbusters in the history of medicine. Statins include products like rosuvastatin (Crestor), atorvastatin (Lipitor) or simvastatin (Zocor) and if you think they are so massively prescribed because they are wildly effective in saving us from the dangers of cardiovascular disease, you’re in for a rude shock. I would be at a loss to find a more misunderstood, overused and misused class of drugs on the planet. In fact, if you are too tired to keep reading and you want a soundbite, this sums up my thoughts: “Someday we will look back on society’s zeal for checking and chemically altering our blood cholesterol in the same way we now regard blood letting and purging: a medical barbarity based on ignorance and hubris.”

For an illustration of all the cholesterol foolishness, let me describe Dave. Dave is a friend of mine, 47-years-old, physically fit, a keen cyclist who doesn’t smoke and a healthy specimen. He tells me he had a mini-heart attack when he was younger, but he brushes that episode off with a wave of the hand. Although he came through it just fine, he was told he had high cholesterol and his doctor wanted to bring it down.

Dave was then put on the newest, most widely marketed and likely the most potent statin out there, Crestor. If you are on Crestor, you’ll be glad to know that, last year, the US Food and Drug Administration approved its use in children as young as 10 and earlier this year approved it for people who have normal cholesterol. Go figure.

Like any pharmaceutical, there is a mix of benefit and harm in taking statins and this equation can change radically depending on how much at risk you are to begin with. For someone like Dave, there is actually some proof of the benefits of statins in secondary prevention – people who have had a previous heart attack or heart disease. But how much would the Daves of the world benefit from a daily statin? And how much would they be risking by taking one?

So for the Daves of the world, I have created a guide. Let’s call it “Dave’s Five-point Primer on Cholesterol-lowering.”

How do you compare to an overweight Scot?

Most of the evidence proving the effectiveness of cholesterol-lowering drugs comes from studies on the unhealthiest people you can find. If you want a big bang for your drug studies, you have to study people who are most likely to benefit. The West of Scotland Coronary Prevention Study (WOSCOPS) trial tested the cholesterol drug pravastatin in a group of men who were probably at the highest risk of cardiovascular disease anywhere on Earth: 6,595 overweight Scotsmen aged 45-64 years with extremely high LDLs (levels of the bad stuff). Nearly half of them were smokers and about 20 percent had some kind of established heart disease and had taken either pravastatin or placebo for five years.

What did they find? The statin guys reduced their LDL cholesterol and that’s apparently a good thing. But how many lived longer or were saved from death by heart attack? The difference in death rates between those on the drug and those on the placebo was two percent. Another way to describe this is that your doctor would have to treat 50 men like those fat, unhealthy Scots for five years with pravastatin to prevent one cardiac death. Is that worth pulling out the bagpipes and playing a victory jig? Obviously, if you aren’t an overweight, smoking Scotsman, you will derive even less than a two percent benefit. How much less? Keep reading.

How do healthier people benefit from statins?

What do the other studies say about healthier people and statins? Never make any health decisions based on one study because you want to look at the big picture, right? One meta-analysis published last year in the British Medical Journal examined the 10 highest quality trials of statins (all different brands) in patients who did not have established heart disease. They concluded that the statin patients generally did better in terms of rates of death, heart attacks and strokes. How much better? They describe the benefits in terms of “numbers needed to treat” to prevent one “event.” The percentages are the benefits in the statin takers over the placebo takers. If you treated 174 people for 4.1 years, you would prevent one death (0.6 percent or six in 1,000). If you treated 81 people for 4.1 years, you would prevent one major heart attack (1.2 percent or 1.2 in 100). If you treated 252 people for 4.1 years, you would prevent one major stroke (0.4 percent or about four in 1,000).

What this meta-analysis tells us is that, statistically speaking, patients who don’t have heart disease would be helped by taking statins. But how about the odds – one in 80 or one in 174? Maybe they’re OK for you if you don’t mind swallowing the statin every day for four years and dealing with the side effects, which brings me to the question:

Are these drugs “safe?”

Remember my motto: “Any drug strong enough to have an effect is strong enough to have a side effect.” Like any powerful drug therapy, statins have side effects and adverse effects, some of which can be fatal.

Muscle weakening and muscle pain are among the most well known of all the adverse effects of the statins. A national health survey done in the US found that people who took statins were 50 percent more likely to have back or leg pain. Statin manufacturers state the risks of rhabdomyolysis (the medical term for severe muscle breakdown that can result in kidney failure) on their product labels. Elevated liver enzymes – a sign of liver injury – develop in about one in 100 statin users. Other unpleasant side effects you might see are sleep disturbances, sexual dysfunction, depression, confusion, short-term or “working” memory loss and transient global amnesia.

Another concern is an increased risk of diabetes. The medical journal The Lancet reviewed several major statin studies and found that the drugs increase the risk of developing type 2 diabetes, on average, by nine percent. That’s not good.

What if I stop taking my statin?

If you are like Dave and stop taking your statin, you’ll be considered normal because many people cannot tolerate statins. For Dave, his sore leg muscles couldn’t be explained away by training hard. In fact, athletes have a very low tolerance for statins because of the muscle-weakening thing. In the real world, the number of people who stop taking the drug is huge; one study found that a third of patients quit their statin within a year and within two years, two-thirds of patients will quit. Basically, it’s “normal” to quit taking your cholesterol-lowering drug.

What else should I do?

Even the cholesterol guidelines say lifestyle changes can exert a much more profound effect on the length and quality of one’s life. The key to maintaining your cardiovascular health and avoiding the risk of a heart attack or stroke is consistent: don’t smoke, eat well and exercise regularly. If you are still concerned about your cholesterol (LDL specifically) and are worried about your future risk of heart attack or stroke, your physician should be able to explain the kind of benefit you might expect by taking a statin.

To the Daves of the world, I only have one bit of advice: “Say know to statins!”

Alan Cassels is a drug policy researcher at the University of Victoria and the author of The ABCs of Disease Mongering: An Epidemic in 26 Letters. Read his other writings at www.alancassels.com