The world's best-selling drugs don't help prevent heart disease, a major new review has discovered
If you're aged 50 or over, your doctor may well suggest you start taking a statin drug as part of your daily routine. He will tell you the drug keeps your 'bad' artery-clogging LDL (low-density lipoprotein) cholesterol in check and so can help you live into healthy old age without heart disease. As Oxford professor Sir Rory Collins put it, statins are just one of life's good things that all of us should be routinely taking, whether or not we are a candidate for a heart attack.
And the world seems to agree. In the 30 years since it was launched, annual sales of statin drugs have grown to around lb20 billion ($32 billion); one statin, Lipitor (atorvastatin), holds the record as the best-selling drug in history, with annual sales reaching $12.4 billion in 2008. And in the UK you don't even have to see a doctor to start your statin regime; there's a version sold in pharmacies you can get without a prescription.
But a major new study has discovered that the statin is medicine's equivalent of the Emperor's new clothes. Everyone says the drug protects against heart disease, but the appalling truth appears to be the exact opposite. Far from being miracle life savers, statins seem to be a killer for all but a small group of people.
So how have doctors got it so wrong? Two factors appear to be at play: the deliberate concealing of the true data; and the disputed theory that LDL cholesterol causes heart disease.
The truth is out there
Two researchers at University College Hospital in Galway, Ireland, uncovered the truth this year when they analyzed 55 studies of statin therapy. People taking these drugs weren't living longer-and were just as likely to develop heart disease-as people not taking a statin. Worse, women, diabetics and young people were more likely to develop heart disease if they took a statin.1
And that's the good news, the sort we're allowed to read. Virtually all the research into statins is paid for by their manufacturers-one drug company is spending around lb35 million ($56 million) on one study alone-and researchers have refused to release their data for others to see.
When researchers from the Cochrane Collaboration, an independent research group, analyzed the way statin studies had been put together, they discovered a selective reporting of outcomes and a failure to report adverse reactions, and that existing heart patients had been filtered out of the results.2
Not even wrong
The statin story begins in 1971 at the laboratories of Japanese pharmaceutical company Sankyo. Biochemist Akira Endo was searching for a compound that could lower cholesterol and be better tolerated than the currently available drugs. As cholesterol is regulated and manufactured in the liver by the enzyme HMG-CoA reductase, Endo reasoned there would be some kind of microorganism that could restrict its development.
He found what he was looking for in the fungus Penicillium citrinum, from which he developed the chemical agent mevastatin. Mevastatin never became commercially available because it caused tumours, muscle deterioration and death in laboratory dogs-reactions that have since been seen in people taking mevastatin's modern equivalents-but it nonetheless caught the attention of America's drug giant, Merck. By 1978, Merck's scientists had isolated lovastatin from a different fungus (Aspergillus terreus).
Now Merck had a solution, but no problem-what did cholesterol have to do with heart disease anyway? A few scientists had mooted the possibility of an association, but most heart physicians weren't buying it.
So Merck put its PR machine into overdrive and decided to bypass doctors and go directly to the public. It began a heart health campaign, explaining that we have two types of cholesterol, the 'good' HDL (high-density lipoprotein) and the 'bad' LDL, which builds up in artery walls and eventually causes a heart attack. The good could keep the bad in check, they reasoned, and aside from diet and exercise, statin drugs were a great way to help achieve a healthy cholesterol number.
The facts, though, weren't supporting the PR drive. At around the time Merck's spin doctors-who were soon followed by other drug companies-were telling the public about their bad cholesterol, the Framingham heart health study was reporting that people over the age of 50 were more likely to die from cardiovascular disease if their cholesterol levels were falling.3
This surprising association was repeated years later when researchers noted that men in Honolulu, Hawaii, with low cholesterol levels were 1.6 times more likely to die prematurely than those with higher levels. "Long-term persistence of low cholesterol concentration actually increases the risk of death," they concluded.4
Begging the question
As other researchers have discovered, cholesterol is vital for the healthy functioning of the body. It influences energy, immunity, fat metabolism, thyroid activity, liver synthesis, stress tolerance, adrenal function and-increasingly as we age-brain function. High cholesterol levels have been found to be protective in elderly patients with heart failure.5
If cholesterol is important for healthy body functioning, then it's perhaps not surprising to find that statins-which can indeed lower cholesterol levels-don't help us live longer.
The Irish researchers, in their trawl of the published literature, couldn't find any studies that conclusively proved that statins added years to our lives. One study found that men aged 69 and older derived no benefit from taking statins. They didn't live longer and they didn't suffer fewer heart attacks.6
Some studies even suggested that statins could hasten death. The drugs triple the risk of coronary artery calcification, when high deposits of calcium settle in the arterial walls-a problem usually associated with high cholesterol levels (which the statins supposedly lower). And medicine's "best kept secret", according to the researchers, was the Illuminate trial, which was stopped early after a statin taken with or without an HDL-raising drug was found to be killing the participants, who were developing cancer or dying suddenly.7
They also found evidence that statins increased the risk of diabetes, cataract formation and muscle weakness, and that the drugs can cause cancer and neurodegenerative disease in
Cholesterol is important for our healthy functioning, but so too is coenzyme Q10 (CoQ10). It's important for maintaining muscle strength, especially those of the heart. CoQ10 and cholesterol share the same pathways, so when you interfere with cholesterol production in the liver, you do the same with CoQ10.
If low levels of CoQ10 cause heart failure and statins block the production of this nutrient, this may explain why statins have been associated with heart disease.
This link has been known for years and, at one stage, Merck applied for a patent to add CoQ10 to its statins, but never acted upon it.
Statins aren't entirely without merit. Middle-aged men with an existing heart condition seem to be better off taking the drugs, but that's about all. For the rest of us, they won't help protect us against heart disease, but might even cause it or any of a range of other side-effects.
Quite a testament for the best-selling drugs of all time.
What's your score?
Many people with an interest in their own health seem to know their 'cholesterol number'. The ideal score, according to the current medical thinking, is 5 mmol/L (millimoles per litre of blood), comprising 1.3 mmol/L of HDL and 3.7 mmol/L of LDL cholesterols, although doctors like to see the HDL score at 2 or higher.
The typical cholesterol score in the UK is more like 6.1, while any LDL reading of 4 or more will trigger an automatic prescription for a statin.
But, as with most things in medicine, your total cholesterol score is the stuff of fashion. Twenty years ago the 'healthy' score was 7; this fell to 6.5 around 10 years ago and, today, any reading above 5 will have the doctor reaching for his prescription pad.
The downward trend is relentless. Doctors are predicting the new healthy score will soon be 4-which it already is for anyone who has suffered a heart attack-and it's expected to fall to just 2.5 over the next decade.
All good news for the statin manufacturers.
So what causes heart disease?
If around half the people dying from heart disease have normal cholesterol levels, and cholesterol is vital for our health as we get older, then what's really causing the current epidemic of heart problems?
One major international investigation, the Interheart Study, discovered that "persistent severe stress" increases the risk of heart attack by two and a half times.1
While all of us suffer stress from time to time-such as when we're rushing to catch a train or to meet a work deadline-the type that leads to heart disease is when we feel powerless, socially isolated or there's no end in sight to the problem.
Dr Malcolm Kendrick has listed the types of stress he thinks cause heart disease, and they include:
o bullying boss
o long-term money worries
o poor social network and feeling 'dislocated' from others
o unloving or abusive spouse.2
1. Lancet, 2004; 364: 937-52
2. Kendrick M. The Great Cholesterol Con: The Truth About What Really Causes Heart Disease and How to Avoid It. London: John Blake Publishing, 2007
3. Open Journal of Endocrine and Metabolic Diseases, 2013; 3: 179-85
4. Cochrane Database Syst Rev, 2011; 1: CD004816
5. JAMA, 1987; 257: 2176-80
6. Lancet, 2001; 358: 351-5
7. Vascular, 2012; 20: 243-50
8. Lancet, 2007; 369: 168-9
9. N Engl J Med, 2007; 357: 2109-22