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