New research shows that statins do not cause the majority of conditions listed in their package leaflets, including memory loss, depression, sleep disturbance, and sexual and erectile dysfunction. 

The study, published in The Lancet, was led by researchers at the University of Sydney and Oxford Population Health. The team gathered data from more than 150,000 participants in 19 large-scale randomised studies from the Cholesterol Treatment Trialists’ Collaboration, which compared the effects of statin therapies against a placebo (or dummy tablet) and four trials comparing the effects of high-intensity versus regular statin dosing. 

Professor Anthony Keech, senior author, and Principal Research Fellow and Director of Cardiovascular Research at the NHMRC Clinical Trials Centre at the University of Sydney said: “Although statins are highly effective at lowering ‘bad’ cholesterol and reducing the risk of cardiovascular disease in both men and women, concerns about their side-effects have persisted.

“But using data from large, randomised placebo-controlled trials, our research provides the best evidence that statins do not cause most of the side effects listed in product leaflets.”

Comparing the number of reports for conditions commonly listed as possible side effects on statin package leaflets, the researchers found there were similar numbers of reports amongst those taking the statin as those taking the placebo.

For example, each year, the number of reports of cognitive or memory impairment was 0.2 percent in those taking the statins, but also 0.2 percent 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 and that statin therapy caused muscle symptoms in only 1 percent 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.

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.

Professor Garry Jennings, Chief Medical Advisor at the Heart Foundation, said: “Over two 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.”

Declaration:

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. CTT’s work is overseen by an independent oversight panel.

*There were also very small increases in risk (less than 0.1 percent) 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.