A cry from the heart

Cholesterol-busting statins were hailed as modern wonder drugs. Now some doctors are not so sure, reports Jerome Burne

Are you male and over 55? If you are female, are you overweight or do you smoke? If the answer is yes, according to the latest medical advice you should pop down to your local pharmacy, buy a packet of the cholesterol-lowering drug Zocor and take it for the rest of your life.

Are you male and over 55? If you are female, are you overweight or do you smoke? If the answer is yes, according to the latest medical advice you should pop down to your local pharmacy, buy a packet of the cholesterol-lowering drug Zocor and take it for the rest of your life.

Dr John Reckless, the chairman of cholesterol-awareness society Heart UK and a consultant endocrinologist at Bath University, claims that this course of action will cut your risk of having a heart attack by about 30 per cent. Recently Dr Reckless recommended putting such drugs (known as statins) in the water supply, arguing that that they are effective and extremely safe.

Since August, if your doctor has not considered your risk of heart disease high enough to write a prescription, you have been able to buy Zocor (otherwise known as simvastatin) over the counter. An ad campaign supporting it has just begun. But could the current enthusiasm for statins be driven by commercial interests and based on misinterpreted data? Last week, a number of senior medical figures went public with detailed concerns that the widely accepted benefits of statins are exaggerated.

Their worries were set out in an open letter to the American National Institutes of Health and the National Cholesterol Education Program that called for a radical rethink of the guidelines for statin use. Signed by more than 30 researchers and clinicians from prestigious universities and medical centres including Harvard, Cornell and Johns Hopkins, it makes two startling claims: that there is no evidence for statins benefiting women who have not had a heart attack, and that lowering the cholesterol levels of elderly patients increases the risk of their getting other diseases such as cancer.

Similar concerns about the value and safety of statins have been raised before, but always by individual researchers. One such critic is Professor Tom Saunders, a nutritionist at King's College London who opposed Dr Reckless's statins-in-the-water idea. He claims that the drugs have "significant" side effects, and casts doubt on their value for patients who have not suffered a heart attack. "The benefit is really confined to people at high risk," he says. "We have no trials on the effect of giving them to low-risk groups."

Another critic has been Dr John Abramson of Harvard Medical School, who was quoted in the BMJ last week opposing a plan to allow statins to be sold over the counter in the US. "In primary prevention [ie people without heart disease], statin therapy does not significantly reduce mortality or the overall risk of serious illness," he said.

The NIH letter is a significant step, as it represents the first time that opponents of statin therapy have joined forces. "It takes a lot of guts for mainstream academics to put their head over the parapet on this one," says one of the two UK signatories, the Cheshire GP Malcolm Kendrick, who has long been publicly sceptical about the value of cholesterol as a useful marker for heart disease.

The letter was in response to the National Heart, Lung and Blood Institute's 2001 cholesterol education programme, which recommended that statins be prescribed for women at moderately high risk of heart disease, on the grounds that six studies had shown that the drugs would reduce their risk of having a heart attack. The NIH letter asserts: "Not one of the six studies provides significance evidence to support this claim. The guidelines admit that studies supporting this recommendation 'generally are lacking' (meaning they don't exist)." The letter also claims that in one study, looking at women with several risk factors but no history of heart disease, the risk of heart attack among those treated with statins actually increased by 10 per cent.

It is part of a wider challenge to the medical authorities. This week, the FDA recommended that SSRIs (a type of antidepressant) should come with a "black box warning". For 10 years, professional psychiatric bodies and drug companies have claimed that SSRIs are safe and effective in preventing suicide. But trial results that critics claimed had been ignored or suppressed finally convinced the FDA that adolescents treated with the drugs were, in fact, more likely to become suicidal.

The signatories to the NIH letter obviously suspect similar spinning with statins. Mirroring another issue raised by the SSRI safety saga, they are also concerned that eight of the nine authors of the updated guidelines for cholesterol management issued last July have financial relationships with drug companies. As a result, they have called for "an independent review free of conflicts of interest to review all the data".

Meanwhile, what can the rest of us do? Neither doctors nor patients can be expected to delve into clinical trial data, but more and more women are being advised to take statins to prevent heart disease. Should they? Side effects are a major consideration, and problems with muscle weakness are well-known.

Far less familiar, and far more controversial, is the danger of birth defects. A red flag was raised on this issue back in April via a short letter in The New England Journal of Medicine, which looked at 52 cases where women taking statins had given birth to severely malformed children. "We found that the patterns of malformations were similar to those found in animals with a problem of cholesterol synthesis," says Dr Robin Edison of the National Institutes of Health in Bethesda. "Cholesterol is vital to the development of nerves, and cholesterol-lowering statins can cross the placenta." There is a standard warning on statins that they should not be taken during pregnancy, but Dr Edison thinks it should be stronger.

Until the many question marks hanging over statins are resolved, those who don't have heart disease can try the alternatives. These include eating healthily, exercising, lowering levels of inflammation with omega-3 oils, reducing homocysteine levels with B vitamins and developing ways to handle stress. All are effective, and much less likely to come with side effects.