Large trials show statins rarely cause reported side effects

Cardiovascular disease results in around 20 million deaths worldwide and causes around a quarter of all deaths in the UK. Statins are highly effective drugs that lower LDL ("bad") cholesterol levels and have been repeatedly proven to reduce the risk of cardiovascular disease. However, there have been concerns about possible side effects.

The researchers gathered data from 23 large-scale randomised studies from the Cholesterol Treatment Trialists' Collaboration: 123,940 participants in 19 large-scale clinical trials comparing the effects of statin therapies against a placebo (or dummy tablet), and 30,724 participants in four trials comparing more intensive versus less intensive statin therapy.

They found similar numbers of reports for those taking the statins and those taking the placebo for almost all the conditions listed in package leaflets as possible side effects. For example, each year, the number of reports of cognitive or memory impairment was 0.2% in those taking the statins, but also 0.2% in those taking the placebo. This means that while people may notice these problems whilst taking statins, there is no good evidence that they are caused by the statin.

Key findings:
• There was no statistically significant excess risk from statin therapy for almost all the conditions listed in package leaflets as potential side effects.
• Taking a statin did not cause any meaningful excess of memory loss or dementia, depression, sleep disturbance, erectile dysfunction, weight gain, nausea, fatigue or headache, and many other conditions.
• There was a small increase in risk (about 0.1%) for liver blood test abnormalities. However, there was no increase in liver disease such as hepatitis or liver failure, indicating that the liver blood test changes do not typically lead to more serious liver problems.

Christina Reith, Associate Professor at Oxford Population Health and lead author of the study, said 'Statins are life-saving drugs used by hundreds of millions of people over the past 30 years. However, concerns about the safety of statins have deterred many people who are at risk of severe disability or death from a heart attack or stroke. Our study provides reassurance that, for most people, the risk of side effects is greatly outweighed by the benefits of statins.'

Previous work by the same researchers established that most muscle symptoms are not caused by statins; statin therapy caused muscle symptoms in only 1% of people during the first year of treatment with no excess thereafter. It has also shown that statins can cause a small increase in blood sugar levels, so people already at high risk may develop diabetes sooner. 

These findings are hugely important and provide authoritative, evidence-based reassurance for patients. Statins are lifesaving drugs, which have been proven to protect against heart attacks and strokes. Among the large number of patients assessed in this well-conducted analysis, only four side effects out of 66 were found to have any association with taking statins, and only in a very small proportion of patients. 

This evidence is a much-needed counter to the misinformation around statins and should help prevent unnecessary deaths from cardiovascular disease. Recognising which side effects might genuinely be associated with statins is also important as it will help doctors make decisions about when to use alternative treatments.'

Professor Bryan Williams, Chief Scientific and Medical Officer at the British Heart Foundation

Professor Sir Rory Collins, Emeritus Professor of Medicine and Epidemiology at Oxford Population Health and senior author of the paper said 'Statin product labels list certain adverse health outcomes as potential treatment-related effects based mainly on information from non-randomised studies which may be subject to bias. We brought together all of the information from large randomised trials to assess the evidence reliably. Now that we know that statins do not cause the majority of side effects listed in package leaflets, statin information requires rapid revision to help patients and doctors make better-informed health decisions.'

All of the trials included in the analyses were large-scale (involving at least 1,000 participants) and tracked patient outcomes for a median of nearly five years. The trials were double-blind, meaning that neither the trial participants nor those managing the participants or leading the study knew who was receiving which treatment, to avoid potential biases due to knowledge of treatment allocation. The list of possible side effects was compiled from those listed for the five most commonly prescribed statins.

The study was conducted by the Cholesterol Treatment Trialists' (CTT) Collaboration, a joint initiative coordinated between the Clinical Trial Service Unit & Epidemiological Studies Unit, Oxford Population Health, and the National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Australia, on behalf of academic researchers representing major statin trials worldwide.
The work was funded by the British Heart Foundation, UKRI Medical Research Council, and the Australian National Health and Medical Research Council. The work of the CTT is overseen by an Independent Oversight Panel.