Statins are still controversial

Even if you don’t take a statin now, it might not be long before you do. The pills, which lower the levels of harmful cholesterol (low-density lipoprotein, or LDL) associated with heart disease and strokes, constitute the most commonly prescribed class of drugs in the UK. They work by disrupting the production of cholesterol in the liver.

As their ubiquity grows, so does the controversy surrounding them. A minority of people, especially women, report side effects such as muscle pain. This week, a paper was published exploring the implications of the National Institute for Health and Care Excellence (Nice) cholesterol guidelines, which recommend statin therapy for anyone with a 10 per cent risk of developing cardiovascular disease (CVD) within the next 10 years.

If these guidelines were followed to the letter in England, according to the paper in the British Journal of General Practice, then an astonishing 11.8m people aged between 30 and 84 would be eligible for statins.

Actually, it becomes less astonishing when you realise that Nice’s risk threshold folds in pretty much all men over 60 and all women over 75, regardless of existing health and lifestyle factors. England, like the rest of the UK, has an ageing population — and one of the biggest predictors of CVD is age.

What is more interesting is that about 9.8m of them have never had a heart attack or stroke. Many of those as-yet-unafflicted folk are likely to sail through another decade without cardiovascular incident. Given the possibility of side-effects, says the Royal College of General Practitioners, dispensing statins so prodigiously would end up with people being needlessly medicalised and possibly even harmed.

The college took particular aim at the way CVD risk is calculated, using an algorithm called QRISK. In response to the paper, Professor Helen Stokes-Lampard, chair of the RCGP, said: “We need to get the risk scores right. If we find that all men over 60 and all women over 75 are going to be eligible for statins with new risk scoring, regardless of any other risk factor, then it should ring alarm bells — because it is not clear that every 60-year-old man or 75-year-old woman is going to benefit from statin therapy.”

As well as warning of the dangers of over-treatment, she pointed out the extra NHS workload and expense that might accrue from people sprinting to their doctors for a prescription.

An almost identical debate about risk and treatment guidelines is happening in the US. The American College of Cardiology, together with the American Heart Association, sets the bar at a 7.5 per cent risk over 10 years. The US Preventive Services Task Force, an influential government-appointed panel that reviews clinical evidence, issued more stringent recommendations last year. Statins, it concluded, best served those who had a 10 per cent risk and another qualifying condition, such as diabetes or hypertension.

Opting for statins means making a commitment to take a daily medicine for the rest of one’s life. The decision lies with the patient, usually in discussion with his or her GP. But the estimate of an individual’s risk is a different issue from whether statins actually work. So, we might usefully ask: do they deliver clinically meaningful benefits?

According to a major review published last year in The Lancet, the answer is a resounding yes. For every 10,000 people on an average dose of 40mg for five years, around 1,000 people with existing diagnoses are protected against further heart attacks and stroke (so-called secondary prevention). Further, the review suggests 500 people are protected from having their first incident (primary prevention).

What of the side effects? The same regimen would produce up to 100 new cases of diabetes, around five cases of myopathy (muscle weakness; this can, rarely, lead to severe complications), and up to 10 haemorrhagic strokes (strokes resulting from an internal bleed). Professor Rory Collins, from the University of Oxford, who led this review, concluded that the benefits of statins had been underestimated and the side-effects overplayed.

Interestingly, the link between statins and muscle pain — widely reported in the media — partially evaporates on closer inspection. In May, another study in The Lancet comparing the frequency of adverse events during different sorts of clinical trials showed that patients seemed to be heavily influenced by negative expectations of the drug: a large proportion of those reporting muscle pain were actually on a placebo, rather than the statin. This fascinating phenomenon, known as the nocebo effect, suggests that, out in the real world, some ailments, though genuine, are incorrectly attributed to statins.

Prof Collins, a vocal public champion of statins, doesn’t have it all his own way. In March, Dr Fiona Godlee, editor of the British Medical Journal, argued that there are still uncertainties relating to the health benefits of statins for those unaffected by CVD.

She also points out that much of the data on which Prof Collins based his positive review came from industry sponsors and is not available for independent, outside scrutiny. Dr Godlee asks: “Why . . . should statins be singled out in calls for independent review of the raw data? Because they are already the most widely prescribed class of drug in high-income and middle-income countries, and because proposals for even wider prescription have sparked justifiable controversy . . . when unabridged internal clinical study reports containing anonymised patient-level data are scrutinised by fresh expert eyes, new information and uncertainties emerge . .. ”

There may be good reasons, other clinicians say, for a person aged over 75 who has never had CVD to be wary of statins: they might be coping with other illnesses and on multiple drugs already (the more medicines a patient takes, the higher the risk of harmful drug interactions). Dissenting voices counter that since statins confer long-term benefit, people are better off starting them pre-emptively.

The non-industry StaREE (Statins for Reducing Events in the Elderly) trial in Australia will report on exactly this patient group — over-75s without CVD — in 2020. While statins undoubtedly benefit those already suffering, the therapy’s effectiveness among low-risk groups — who can also change their lifestyle in pursuit of health — remains a live question.

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