Statin side effects are ‘overdiagnosed’, with fewer than 10% of patients experiencing them, a large review of the research has concluded.
Researchers carried out a meta-analysis of 176 studies with over four million patients worldwide, with the aim to identify the overall prevalence of statin intolerance, as well as the prevalence according to different diagnostic criteria, and what factors might place people at greater risk of statin intolerance.
Overall, they found that prevalence was 9.1% although this reduced when using diagnostic criteria from the National Lipid Association, the ILEP and the European Atherosclerosis Society to 7%, 6.7% and 5.9% respectively.
The researchers said that until now it was not clear what proportion of people were truly intolerant, with ‘inconsistent reports’ from studies, randomised controlled trials and databases that suggested it could range from 5-50%.
Lead researcher Professor Maciej Banach, of the Medical University of Lodz and the University of Zielona Góra, Poland, said the results ‘show that in most cases statin intolerance is overestimated and overdiagnosed, and they mean that around 93% of patients on statin therapy can be treated effectively, with very good tolerability and without any safety issues’.
He added: ‘Our findings mean that we should evaluate patients’ symptoms very carefully, firstly to see whether symptoms are indeed caused by statins, and secondly, to evaluate whether it might be patients’ perceptions that statins are harmful – so-called nocebo or drucebo effect – which could be responsible for more than 50% of all symptoms, rather than the drug itself.’
The researchers acknowledged research limitations including differences between patients included in different studies and lack of information on the amount of alcohol consumption and types of exercise.
But Professor Banach said: ‘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.’
The ‘most important message to patients as a result of this study’, he said, ‘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’.
‘The same clear message can be addressed to physicians treating patients with high cholesterol levels. 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.’
However, commenting on the study, Professor Riyaz Patel, professor of cardiology at UCL and consultant cardiologist at Barts Health NHS Trust, cautioned that in the analysis ‘only 200,000 or so patients were from trials and four million from cohorts’.
‘This doesn’t make the analysis unreliable but needs to be considered, especially as the overall effect suggested that statin side effects were much lower in trials and higher in cohorts indicating differences in the two settings.
‘It is possible more people reported side effects in the cohorts which may not truly be statin side effects and people who were less likely to report side effects and underwent enrolment screening procedures were participating in trials.’
But he added: ‘Clinically, it should be stated that some patients do experience real side effects and we do our best to help them with alternative therapies as with any other medicine.’
Risk factors for statin side effects
In terms of who is more likely to experience side effects, increased risk was observed among patients who were older, female, of Black or Asian race, obese, or suffering from diabetes, under-active thyroid glands, or chronic liver or kidney failure.
Other risk factors included co-prescribing with arrhythmia drugs, calcium channel blockers, alcohol use and higher statin doses.
In these groups, the increased risk ranged from 22% from high alcohol consumption and 48% from being female.
Professor Banach commented that 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 use of innovative new drugs,’ he said.