Statins to reduce heart attacks or strokes

Chris Street edits in bold.

New Scientist magazine (7th October 2006) reports on the use of Statins to reduce heart attacks or strokes.

"So you think you're healthy? You are in your 40s, feel right as rain, normal blood pressure, normal cholesterol, pretty good diet, occasional exercise. How would you react if your doctor suggested you take a powerful drug every day for the rest of your life? The drug, known as a statin, will lower your cholesterol even further and reduce your risk of a heart attack or stroke.

According to one recent estimate, most men and many women over 40 could benefit from the drugs.

If you are worried about side effects, your doctor will reassure you that a meta-analysis that pooled data from 14 trials involving more than 90,000 people shows the treatment is very safe.

The same study suggests that even if your cholesterol level is normal, taking a statin can still reduce your cardiovascular risk. And the greater your risk - if you smoke, suffer from high blood pressure or diabetes, or have a family history of heart disease, for example - the greater the potential benefits."

New Scientist says "Lowering cholesterol is beneficial in pretty much everyone who has been studied," says Colin Baigent, who coordinated the meta-analysis by the Clinical Trial Service Unit (CTSU) at the University of Oxford. "It doesn't really matter what the cholesterol level is. It could be average or even low, but if you reduce it even further in a person who is at high risk you get benefits." Statins also have anti-inflammatory properties, and have shown promising results when used to treat diseases like rheumatoid arthritis, multiple sclerosis and Alzheimer's. Some research even suggests they can help tackle viral infections such as hepatitis C and HIV.

Can any drug really be that good? As enthusiastic doctors put ever more people on statins, sceptics are warning that we don't know enough about the possible adverse effects of taking them over a lifetime.

Others claim that statins' potency against heart disease has little to do with lowering cholesterol and instead results from their anti-inflammatory properties, leading some to dismiss them as "expensive aspirin". So could the rush to put millions more people on statins be a costly mistake?"

"The association between cholesterol, its transport in the bloodstream by a protein called low-density lipoprotein and heart disease is fairly well established. Cholesterol in the form of LDL, so-called "bad cholesterol", can infiltrate the walls of coronary arteries, contributing to the formation of a fibrous plug of immune cells called a plaque. If this ruptures it can trigger the formation of a blood clot that blocks the artery and starves the heart of oxygen - a heart attack, in other words. Equally disastrously, the clot can break free and block arteries in the brain, triggering a stroke."

"Some doctors, however, are alarmed by the trend towards dishing out statins to millions more people and giving higher dosages to lower cholesterol even further. They say the benefits for those who do not already have heart disease are small, while the potential risks are largely unknown. "What price should you pay for a modest effect?" Sutter asks. "The price shouldn't be very high because the effect is weak at best." A 20 per cent reduction in cardiovascular risk may sound impressive, but it doesn't look quite as good when you realise what it means for each individual: if your risk of having a heart attack over the next five years is 5 per cent, say, then taking statins will reduce it only to 4 per cent."

"Sutter and others say that statin researchers have failed to report adverse effects in enough detail to allow doctors and patients to weigh the potential costs against the benefits. "There's no good reporting of adverse effects at high doses and very modest reporting even at moderate doses," Sutter says. "If you are prescribed a statin, the doctor expects you to take it for the rest of your life," says Uffe Ravnskov, an independent researcher and former hospital doctor based in Lund, Sweden, who runs The International Network of Cholesterol Skeptics. He claims almost half of patients have adverse effects."

"Alleged side effects include memory loss, extreme irritability, aggression, suicidal impulses and impotence. Evidence for these remains sketchy, however, coming from small trials and case studies. Statins do cause liver damage in around 1 per cent of patients, but this should be picked up by routine liver function tests and can be reversed by coming off the drugs. It is also clear that statins can damage muscles. As many as a fifth of people taking the drugs in trials say they experience some muscle weakness or pain, and exercise seems to make things worse. These symptoms are commonplace anyway in middle-aged and elderly people, however, and a similar number of patients taking a placebo also report them. So it is difficult to determine the exact extent of the problem. "

"In very rare cases statins cause rhabdomyolysis, a severe form of muscle damage in which the breakdown products cause kidney failure. The rate was especially high with cerivastatin (Baycol), which caused 50 deaths and was withdrawn in 2001. "

"Confusingly, some small studies have hinted that statins increase the risk of cancer while others suggest they may guard against it. The CTSU meta-analysis found no association between cancer and statins, and a similarly large study from the US, which looked at 26 trials involving 87,000 patients, also found no link."

"Most trials, though, have lasted only five years or less. For some this leaves lingering doubts. "You don't get lung cancer after smoking for 10 years; it takes much longer to show up," Ravnskov points out. "Heavy smokers get lung cancer in their 50s and 60s and they have smoked for decades before that." Nevertheless, White, who led the US study, is confident that even after five years some signs of increased cancer risk would show up in trials. "Within the period we were looking at you should at least have started to see some trends," he says. "

"The crucial issue now facing policy-makers is how and where to draw the line that defines who should be offered statins. In the US and Canada, prescribing guidelines focus on lowering cholesterol below certain thresholds, depending on the individual's overall risk of a heart attack or stroke. The lowering of the US target levels in 2004, which is leading to millions more people being put on statins, sparked controversy when it was revealed that eight out of the nine experts involved had ties to statin manufacturers. "

"In Australia, New Zealand and the UK, the emphasis is on treating those with the highest overall risk rather than on cholesterol targets. This year, a Canadian study that modelled the effects of applying the various guidelines concluded that the high-risk approach is more effective in terms of number of lives saved per number treated (BMJ, vol 329, p 529). It found, for instance, that applying the US guidelines would result in twice as many people taking statins as the New Zealand guidelines without preventing any more deaths. "

"Yet even the more conservative guidelines will lead to millions more people taking statins for the rest of their lives, often starting younger or being given higher doses. You could be one of them. If the advocates of statins are right, this policy will come to be seen as a triumph for preventative medicine, saving tens of thousands of lives. If the critics are right, for those with a low risk of heart disease statins could do more harm than good. Which will you bet your life on when your doctor mentions the s-word? "