News release

From: University of Oxford

Statins do not cause the majority of side effects listed in package leaflets

Statins do not cause the majority of the conditions that have been listed in their package leaflets, including memory loss, depression, sleep disturbance, and erectile and sexual dysfunction, according to the most comprehensive review of possible side effects. The study was led by researchers at Oxford Population Health and published in The Lancet.

Cardiovascular disease results in around 20 million deaths worldwide. Statins are highly effective drugs that lower LDL (“bad”) cholesterol levels and have been repeatedly proven to reduce the risk of cardiovascular disease and shown to reduce mortality in both men and women. 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 frequency 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 largely 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.

Professor Garry Jennings, Chief Medical Advisor at the Heart Foundation, said ‘Over 2 million Australians are prescribed statins to prevent heart attacks, stroke and other conditions, potentially providing each person with lifelong benefit. As consumers and health professionals we have too readily blamed everyday symptoms including aches and pains, small biochemical changes, and forgetfulness, on statin therapy. This important study confirms that most of these symptoms are due to other causes as true statin intolerance is rare. It should encourage people to keep taking statins in line with national guidelines.’

Anthony Keech, Cardiologist at Royal Prince Alfred Hospital, and Professor of Medicine, Cardiology and Epidemiology at the University of Sydney, and an author of the paper said ‘Although people may experience problems whilst taking statins, using the most reliable evidence from large randomised placebo-controlled trials provided the best evidence that statins do not cause most of the side effects listed in product leaflets.’

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.

ENDS

Notes to editors:

*There were also very small increases in risk (less than 0.1%) for medical issues that involved changes in urine, and oedema (a build-up of fluid in the body typically causing swelling in the ankles, feet and legs) in the trials of statin versus placebo, but analysis of the four trials of more intensive versus less intensive statin therapy showed no significant excess risk for these changes, suggesting these excesses were not real.

Post-publication link: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01578-8/fulltext

For further information on the methods used in this study, see: Cholesterol Treatment Trialists’ Collaboration. Harmonisation of large-scale, heterogeneous individual participant adverse event data from randomised trials of statin therapy. Clinical Trials. 2022;19(6):593-604. doi:10.1177/17407745221105509.

About the Cholesterol Treatment Trialists’Collaboration

The Cholesterol Treatment Trialists’ (CTT) Collaboration was established in 1994, with its initial protocol being published in 1995. It was set up after it was recognised that no single lipid intervention trial would be likely to have a sufficient number of trial participants (and hence statistical power) to reliably assess mortality outcomes or look at events in particular types of patient. It conducts meta-analyses of large-scale (at least 1000 participants), long-term (at least two years scheduled treatment duration) un-confounded, randomised controlled trials of lipid intervention therapies.

The collaboration involves approximately 150 doctors, statisticians and research scientists, including experts in the field of cardiology, epidemiology, lipidology and clinical trials, from across the world. Although individual trials that are contributing data to the analyses were funded by the pharmaceutical industry, as well as by charities and government organisations, the CTT Collaboration has not received grant funding from industry.

About Oxford Population Health

Oxford Population Health (the Nuffield Department of Population Health) is a world-leading research institute, based at the University of Oxford, which investigates the causes and prevention of disease. Oxford Population Health brings together a number of world-leading research groups, including the Clinical Trial Service Unit and Epidemiological Studies Unit and other groups working on cancer epidemiology, demographic science, health economics, ethics, and health record linkage. It is also the lead partner in the Oxford University Big Data Institute.

About the NHMRC Clinical Trials Centre

The National Health and Medical Research Council (NHMRC) Clinical Trials Centre (CTC) at the University of Sydney is a globally recognised flagship centre of excellence in clinical trials research, with over 35 years of experience designing, coordinating and delivering high-impact studies that improve health outcomes and inform clinical practice and policy. Established in 1988, the CTC brings together world-class expertise in trial methodology, biostatistics, health economics, data management and evidence synthesis, working across a wide range of therapeutic areas with national and international partners. With a proven track record in conducting hundreds of clinical trials involving tens of thousands of participants and collaborations with leading research organisations, the Centre’s work continues to drive innovation, address unmet clinical needs and advance best practice in healthcare.