The truth about the safety of statins

If you were offered a potentially life-saving drug, free on the NHS, is there any doubt you would refuse it? With experts increasingly realising that statins are the magic bullets to help halt the alarming rise in heart deaths, new draft guidance issued earlier this year said people as young as 25 should be taking the cholesterol-busting drugs to ward off heart attacks and strokes.

In January 2023, the National Institute for Health and Care Excellence (Nice) watchdog which provides guidelines for the NHS, released a set of new recommendations suggesting that statins should be rolled out on a far wider scale for those at risk of cardiovascular disease.

Around 10 million people in England are currently eligible for the cholesterol-lowering drugs but Nice has recommended widening the window of eligibility to encompass those between 25 and 84 who are deemed to have a 10 per cent or higher risk of a cardiovascular event in the next decade. It would mean that up to 25 million people could receive statins, with the aim of preventing the onset of cardiovascular disease, a set of chronic illnesses that are responsible for one in four deaths.

Sir Nilesh Samani, medical director of the British Heart Foundation and a cardiology professor, says it is without question that statins are life-saving drugs for patients with existing heart disease. 

“If you had a heart attack or a stroke, or you suffer with coronary heart disease or angina, then the evidence basis is not controversial at all,” he says. “Everyone would recommend those patients to take them. In terms of people who haven’t got an established disease, the statin recommendation is based on an assessment of their risk over the next ten years.”

One group of patients who could particularly stand to benefit from preventative statins is the estimated 250,000 people in the UK who have a condition known as familial hypercholesterolemia, which means they have high cholesterol from birth. A 2019 study that followed 214 patients with the condition for 20 years, after they began receiving statin therapy as children, found that it reduced their cholesterol by an average of 32 per cent and reduced their risk of cardiovascular disease in adulthood.

However, not everyone is able to tolerate the drugs and scientists are still learning more about some rare statin-induced side effects. The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) recently revealed that between 1995 and 2023, there have been 10 cases of a neuromuscular disorder known as myasthenia gravis, which may have been triggered by statins.

But Samani points out that given the many millions of people who take statins – 9.5 million people were prescribed them in 2022 – it is hard to draw conclusive links between the drugs and such rare isolated events.

“With very rare things, it’s very difficult to attribute them to the drug because so many people are on statins,” he says.

So what are statins, and how exactly do they work?

How do statins really work?

Statins are a class of drugs that include atorvastatin, fluvastatin, pravastatin, rosuvastatin and simvastatin. In general, they act to lower the levels of a type of cholesterol known as low-density lipoprotein or LDL cholesterol.

Dr Unnati Desai, national lead for GP services at Nuffield Health, says: “LDL is often referred to as bad cholesterol because elevated levels of LDL are associated with an increased risk of cardiovascular disease.” 

Statins reduce LDL cholesterol through two main mechanisms of action. The first is to block the activity of an enzyme called HMG-CoA reductase, which plays an essential role in how cholesterol is produced in the liver. They also increase the number of LDL receptors on the surface of liver cells, enabling the liver to remove LDL cholesterol from the bloodstream more efficiently.

But while they might work in similar ways, no two statins are the same. They each have distinct chemical structures and vary in potency, dosage and how they are metabolised in the body. High potency statins tend to be offered to patients who have already experienced a serious event such as a stroke or heart attack. “Some are more effective at lowering cholesterol levels than others,” says Dr Desai. “For example, rosuvastatin and atorvastatin are considered high-potency statins and can lower cholesterol more effectively at lower doses compared with moderate-potency statins like simvastatin and lovastatin.”

Statins can be classified as being either fat-soluble or water-soluble which affects how well they are absorbed within the body and their side effect profile. “Fat-soluble statins like atorvastatin and simvastatin, are better absorbed and may have a more substantial effect on cholesterol,” says Dr Desai. “Water-soluble statins, like pravastatin, are less likely to penetrate cells but may be associated with fewer muscle-related side effects.”

But we are still learning more about the other benefits statins can bring to cardiovascular health. For example, earlier this year, a study from Stanford Medicine discovered that simvastatin can improve blood vessel health, which could be why heart failure patients who take statins are less likely to suffer a second heart attack.

Should I be taking statins for my cholesterol?

Based on the new Nice recommendations, NHS doctors will compute a cardiovascular disease risk score for all patients, before offering them the choice of going on statin therapy.

The latest tools used to compute these risk scores are based on AI analysis of the patient’s electronic health records and consider a whole variety of factors, not just cholesterol levels.

“Factors considered also include age, family history of heart disease, smoking status, blood pressure level, and whether they have diabetes or not,” says Dr Gosia Wamil, a cardiologist at Mayo Clinic Healthcare in London. “These newer calculators can improve prediction of who needs to be treated or not.”

How long do statins take to work?

Statins will start to reduce LDL cholesterol within weeks, but it can take several months before their full benefits are apparent. According to Dr Wamil, long-term data indicate that the efficacy of statins remains largely stable over time. “There have been no indications of waning effectiveness observed even after prolonged use over many years, provided that they are consistently and appropriately administered,” she says. “LDL should be monitored, and the statin dose may need to be adjusted occasionally to achieve a good effect.”

Are statins causing my aches and pains?

The most widely cited complaint from taking statins is muscle aches, and having prescribed the drugs for more than 30 years, Sir Nilesh says there is no question that statins are linked to a slightly increased risk of aches and pains.

However, he believes that the degree of media coverage surrounding statin-induced muscle aches has contributed to a medical phenomenon known as the nocebo effect (the opposite of the placebo effect), where the belief that a drug will cause harm ends up triggering negative symptoms.

In one British Heart Foundation study, participants were given a dummy pill or a placebo, which they believed was a statin, and yet they still complained of muscle aches. Last year, a large analysis published in The Lancet estimated that 90 per cent of the time, muscle aches were not related to statins.

“There’s evidence that people have now been conditioned in some way to expect muscle aches with statins,” says Samani. “So anytime they get aches, they think it’s the medicine.”

Are there any other side effects?

In some very rare cases, statins can cause a condition called rhabdomyolysis in which muscle cells break down, releasing a protein called myoglobin into the bloodstream which can clog up the kidneys, resulting in acute kidney failure and other complications.

The early signs of rhabdomyolysis tend to be muscle inflammation, and so people experiencing particularly severe muscle pain after starting on a course of statins should consult their doctor. However, rhabdomyolysis affects only 1.5 in every 100,000 people who take statins.

“Long-term statin use is considered safe and associated with significant benefits in reducing cardiovascular events,” says Dr Wamil. “Regular monitoring and reporting of any unusual symptoms to a healthcare provider are essential but the benefits of long-term statin use in preventing heart attacks, strokes, and mortality often outweighs potential risks, especially for individuals at high risk of cardiovascular disease.”

How much alcohol can I drink with statins?

There are no guidelines against drinking alcohol while taking statins, but Dr Desai suggests discussing your typical weekly alcohol consumption with a health professional before starting on the drugs.

“There’s no absolute contraindication to drinking alcohol when taking a statin, however it is important to drink within the recommended limit of 14 units per week, ensuring alcohol-free days by spreading the drinks over three or more days during the week,” she says.

However, you do have to be slightly careful about grapefruit juice or eating these fruits. This may seem unusual but grapefruit can actually react with certain statins, inducing severe muscle or joint pain. You should avoid them completely if taking simvastatin, while consumption should be minimised when on atorvastatin. Other statins are not known to react with grapefruit.   

Is there an alternative to statins?

For those concerned about whether they will be able to tolerate statins, there is a far wider range of cholesterol-lowering alternatives than ever before.

The most widely used are PCSK9 inhibitors, a class of drugs which includes medications like inclisiran, alirocumab and evolocumab, and have been shown to be capable of reducing LDL cholesterol by around 50 to 60 per cent or more.

PCSK9 inhibitors reduce the activity of a protein called PCSK9 that normally blocks the liver’s cholesterol receptors. By inhibiting this protein, the receptors are able to keep extracting cholesterol from the blood.

“These drugs are usually used as an additive treatment for people whose cholesterol doesn’t come down sufficiently with statins or are statin-intolerant,” says Sir Nilesh.

Dr Wamil says that while they tend to be well-tolerated by patients, the disadvantages are that not everyone likes having to receive regular injections and they come at a higher cost for healthcare providers. “Whether they are better than statins depends on an individual’s specific health circumstances,” she says.

Should I take statins?

Ultimately the question of whether someone should begin taking statins, depends very much on their individual health circumstances.

“For anyone, their risk is a third lower with a statin,” says Dr Iqbal Malik, a consultant cardiologist and medical director of One Welbeck Heart Health in London. “If your risk is near zero, it is not worth it, but if your risk is very high, it is definitely worth it.”

Sir Nilesh Samani says that statin therapy should always be the result of a shared decision-making process between the cardiologist and the patient, and a two-way conversation about their risk of disease and the relative benefits which the drug might be able to offer them.

“There’s always the balance between trying to reduce the total number of heart attacks and strokes, and the issue of medicalising more of the population,” he says. “So it is very much an individual, shared decision-making process. If the patient is a frail 85 year old with multiple other health problems, then a statin might not be the right thing. But if they have a family history of disease, and a 10 per cent risk of having a stroke in the next decade, most doctors would feel that the benefits are probably there.”