The largest study ever conducted into the tolerance of statins has found that intolerance of these drugs is over-estimated and over-diagnosed.

Statins are a widely-prescribed group of drugs used to lower the level of low-density lipoprotein (LDL) cholesterol in the blood. Research suggest that around one-third of people in Ireland over the age of 50 take statins.

However, according to this new study, up to 50% of patients stop taking statins, reduce their dose or take them irregularly because they believe the drugs cause muscle pain and other side-effects.

Until now, it has been unclear what proportion of people are truly intolerant of the drugs, with inconsistent reports from various studies, trials and databases suggesting it could be anything between 5% and 50%.

Researchers from Poland set out to determine the true prevalence of statin intolerance. They carried out a meta-analysis of 176 studies involving over 4.1 million people worldwide.

They found that the overall prevalence of intolerance was 9.1%. However, prevalence was even less when assessed according to diagnostic criteria from the National Lipid Association (7%), the International Lipid Expert Panel (ILEP) (6.7%) and the European Atherosclerosis Society (5.9%).

“These results show that in most cases statin intolerance is over-estimated and over-diagnosed, and they mean that around 93% of patients on statin therapy can be treated effectively with very good tolerability and without any safety issues,” commented lead researcher, Prof Maciej Banach, of the Medical University of Lodz and the University of Zielona Góra in Poland.

He said that these findings shows that symptoms need to be evaluated very carefully “firstly to see whether they are indeed caused by statins and secondly, to evaluate whether it might be patients’ perceptions that statins are harmful - the so-called nocebo or drucebo effect - which could be responsible for more than 50% of all symptoms, rather than the drug itself”.

The researchers found that people who were older, female, of Black or Asian race, obese or suffering from diabetes, under-active thyroid glands, or chronic liver or kidney failure were more likely to be intolerant of the drugs.

Furthermore, a higher risk of intolerance was also linked to drugs to control heart arrhythmia, calcium channel blockers, alcohol use and higher statin doses. The increased risk of statin intolerance ranged from 22% (high alcohol consumption) to 48% (being female) in these groups.

“It is critically important to know about these risk factors so that we can predict effectively that a particular patient is at higher risk of statin intolerance. Then we can consider upfront other ways to treat them in order to reduce the risk and improve adherence to treatment. This could include lower statin doses, combination therapy and the use of innovative new drugs,” Prof Banach pointed out.

The researchers acknowledged some limitations to their meta-analysis, such as differences between patients included in different studies. However, they have attempted to reduce the risk of bias from these and this is helped by the large number of studies and patients included in the analysis.

“I believe the size of our study, which is the largest in the world to investigate this question, means we are able to finally and effectively answer the question about the true prevalence of statin intolerance.

“These results clearly show that patients needn’t be afraid of statin therapy as it is very well tolerated in as much as 93%, which is similar or even better than other cardiology drugs, including ones for reducing blood pressure and clotting or blocking of blood vessels,” Prof Banach said.

He also emphasised that patients “need to know that statins may prolong their life”.

“In cases where side-effects appear, we have enough knowledge to manage these effectively. The most important message to patients as a result of this study is that they should keep on taking statins according to the prescribed dose and discuss any side-effects with their doctor, rather than discontinuing the medication,” he said.

He insisted that this message should also be given to healthcare professionals who are treating people with high cholesterol levels, as most cases of statin intolerance observed in clinical practice “are associated with effects caused by patients’ misconceptions about the side-effects of statins or may be due to other reasons”.

“We should carefully evaluate symptoms, assessing in detail patients’ medical histories, when the symptoms appeared, specific details of pain, other medications the patients are taking, and other conditions and risk factors. Then we will see that statins can be used safely in most patients, which is critically important for reducing their cholesterol levels and preventing heart and blood vessel diseases and death,” Prof Banach added.

Details of these findings are published in the European Heart Journal.