Amid disagreements over the side-effects of statins, Dani Garavelli asks if these controversial life-saving drugs should be more widely prescribed
They were billed as magic bullets: pills that would allow you to eat pizza and chips yet avoid the heart attacks and strokes which are the traditional legacy of a fat-laden diet. And – though they haven’t wiped out the need for lifestyle changes (convincing patients to stop smoking and eat more healthily remains the first priority for GPs when dealing with high cholesterol) – statins are still widely regarded as a wonder-drug.
More than seven million people in the UK now take the tablets which work by lowering the rates of low-density lipoprotein (LDL) cholesterol in the blood, and the figure is set to rise. At the moment they are prescribed to those who have already suffered an episode (secondary prevention) or who are deemed to be at 20 per cent risk of developing cardiovascular disease in the next ten years (primary prevention). However, now that almost all statins are now off-patent, and so cheaper, the National Institute for Health and Care Excellence (NICE) has recommended the threshold should be lowered to 10 per cent, meaning millions more would be eligible to take them.
But not everyone sees the mass- prescription of statins as a boon. While it is broadly accepted within the medical profession that the drugs significantly reduce the risk of heart attacks and strokes in those who have already suffered a coronary episode, opinions are divided over the extent of their effectiveness in preventing them in those with no prior history. And that’s without considering the fierce debate over the scale of drugs’ side-effects which are said to include muscle weakness, possible memory loss and an increase in the risk of developing type-2 diabetes.
As if it wasn’t already confusing enough for patients, the authors of a paper and subsequent article published in the highly-respected British Medical Journal last week retracted figures they had cited on the severity and frequency of side-effects after complaints by Oxford professor Sir Rory Collins that they were wrong.
Professor John Abramson and Dr Aseem Malhotra had claimed an observational study found 18-20 per cent of those taking statins would suffer side-effects, but later admitted these statistics were misleading. The BMJ acted quickly, drawing attention to the retractions, and setting up an independent expert panel to decide whether the articles ought to be withdrawn in their entirety, but the damage may already have been done. “The evidence for statins is strong and robust and the worry about the current controversy that is being stirred up by these BMJ papers is that they’ve raised concerns about side-effects that just aren’t real,” says Professor Peter Weissberg, medical director of the British Heart Foundation.
Though the days when one scaremongering story saw thousands of patients flock to their surgeries seeking an explanation are over, it is quite possible the publicity led some patients to take unilateral action. “These scares come along so often these days, people have become used to them so we don’t tend to get patients phoning up in a panic the way they once did, but they feed into the general feelings people have about statins and their concerns will come out in conversations we have about starting or changing them,” says Dr Alan McDevitt, chairman of the GPs committee of the BMA in Scotland. “And sometimes people don’t come to us for advice, they just stop taking the drugs, which can be dangerous.”
This is not the first time that misleading or erroneous research in a leading medical journal has had serious implications for people’s health. In 1998, a paper written by Dr Andrew Wakefield and published in The Lancet which linked the MMR jab to autism sparked a backlash and led to an instant drop in the number of children given the vaccine and outbreaks of measles.
When the BMJ articles were published earlier this year, Collins suggested the repercussions would be even more far-reaching. Given the speed with which the BMJ has responded, this now seems unlikely. But the problem for patients is that the conflict between the pro- and anti-statin camp remains unresolved. In one corner are experts such Weissberg and Collins, who believe statins should be more widely-prescribed. And in the other, are doctors such as Malcolm Mc-Kendrick – author of The Great Cholesterol Con – who questions whether high cholesterol is, in fact, the key factor in heart attacks and strokes and claims the benefits of statins have been overstated (and their disadvantages understated). In the middle are the baffled patients who have to weigh up the conflicting advice and the GPs who are tasked with advising them.
Although death rates have been decreasing, cardiovascular disease is still the UK’s biggest killer, claiming around 180,000 lives a year. Statins work by slowing the liver’s production of LPL cholesterol and are said by the NHS to save thousands of lives a year.
There’s no doubt the drugs are effective in reducing cardiovascular-related mortality and morbidity in people who already have heart disease. Many large controlled trials have shown risk reductions of more than 20 per cent. One of the first big trials of the drug’s effectiveness in primary prevention was carried out by Professor Stuart Cobbe in the West of Scotland in the early 90s. The study focused on an area with a high incidence of cardiovascular disease and looked at men aged 45-64 with high cholesterol. Here too the results were impressive. More unexpectedly, a ten-year follow-up published in 2007 showed that the reduced risk lasted for years after most of the men involved had stopped taking the drug.
Such findings have led some doctors to claim statins should be available to everyone over a certain age, with a handful even suggesting they should be added to the water supply. Yet others remain unconvinced. They point out trials are often funded by the pharmaceutical companies and tend to quote risk reduction in relative rather than absolute terms. “For the vast majority of people, taking a statin will have zero impact on their life expectancy,” McKendrick has said. “There have not been any trials carried out in the elderly, and there is no evidence any women will benefit from taking them.”
One of the downsides of statins is that they increase the risk of getting type-2 diabetes, but, according to Naveed Sattar, professor of metabolic medicine at Glasgow University, the effect is minimal and can be offset by making lifestyle changes such as losing a few pounds.
Another controversial side-effect is muscle-weakening. Paul Martin, who was on ACE inhibitors for high blood pressure, was prescribed statins during an annual check-up four years ago when he was 62. “I took them for three weeks, then my legs turned to jelly while I was in the bank,” he says. “I thought: ‘wow – that’s unusual’, but I left it. Then the pain got worse. I saw a doctor and he seemed horrified and told me to stop taking them. I did and the issues slowly subsided. I have talked to a lot of people and this doesn’t seem to be an isolated experience.” Martin, who goes to the gym and walks or runs seven miles a day, does not believe he was at high risk of heart disease, but says doctors are keen to treat solely on the basis of age. “I believe statins are lobbed out to my age group irrespective of clinical need, with the best of intentions, but with variable results.”
The difficulty in trying to determine the side-effects of any particular drug is that patients tend to present with a variety of conditions and be taking a variety of medication. In addition, if they are already aware a particular drug is linked with a particular side-effect they may start attributing everyday symptoms to its use.
“If I were to ask if you had experienced a muscle pain in the last month I think you might tell me ‘yes, I have’,” says McDevitt. “Now, if you are not on any drugs, you would blame that pain on not exercising or sleeping in the wrong position, but if you are on statins and knew they could cause side-effects, you might go to your doctor and say ‘are statins causing this?’ and I’d say, ‘they might be’ and you might decide to stop.”
Most patients, the pro-statin doctors insist, will not experience any side- effects and for the 5 per cent who do, changing the dose or the type of statin will end or at least reduce them. Those who continue to experience symptoms have to make a judgment: do the potential benefits outweigh the impact on their quality of life? Clearly this decision will depend on how severe those side-effects are and on their perception of risk. Those who have already experienced a coronary heart attack are likely to be willing to put up with greater inconvenience than those for whom the prospect of getting cardiovascular disease is hypothetical.
The reason the NICE recommendation to reduce the threshold has brought the debate over side-effects to a head is that the lower the risk patients face, the more of them you have to treat before you prevent one heart attack or one stroke. The question is: how low do you have to go before you are doing more harm than good?
“That was their [the BMJ authors’] concern, but since the figures they cited have been debunked I think it is perfectly reasonable for us to carry on concluding that we can lower the threshold,” says Sattar. “I mean, the current threshold is quite high. If you were told you had a one in five risk of having a heart attack or stroke in the next ten years you’d be worried. There will be people who fall just outside the threshold who would like to be on statins.”
The other question is at what point does prescribing statins cease to be cost-effective? While reducing the incidence of cardiovascular disease reduces the burden on the NHS, and the price of the statins themselves has gone down, there are costs attached to assessing which patients ought to be on them.
“The way we currently do statins is we tend to do lots of blood checks and tests and so there is a workload and a cost to the NHS of doing that,” says McDevitt. “It’s a bit pointless doing a risk assessment if almost everyone is going to reach the level of treatment and you are probably getting close to that if you go to 10 per cent. It might be easier to say: ‘let’s not medicalise it, let’s offer statins to everyone over the age of 50 and leave it to the individual’.”
The disadvantage of this, as McKevitt is quick to point out, is that those who need statins the most – those from deprived communities where the incidence of coronary heart disease is high and life expectancy low – will be the least likely to go to a chemist and ask for them.
Even if the BMJ withdraws the two contentious articles in their entirety, as Collins has requested, the debate over the efficacy of statins and how widely they ought to be prescribed is likely to continue. But the weight of medical opinion seems to suggest that for those with moderate to high risk factor they have considerable benefits.
“There are grey zones. We don’t quite know, for example, over 85, how much they are likely to prolong life and there’s some research that suggests maybe not much,” says Sattar. “But for the middle-aged individual who is clearly at high risk because they have high cholesterol and hypertension, statins can generally be used to lower cholesterol in a way which doesn’t give patients side-effects, but will reduce their risks of heart attacks and strokes.” «