Most side effects listed on statin labels may not be caused by the drugs at all.
By University of Oxford
Statins are widely used because they lower LDL (“bad”) cholesterol and have repeatedly been shown to cut the risk of cardiovascular disease.
Still, many people
worry about side effects, especially when symptoms appear after starting a new
medication.
To test whether statins truly cause the long list of problems often attributed to them, researchers pooled evidence from 23 large randomized studies in the Cholesterol Treatment Trialists’ Collaboration.
The analysis included 123,940 participants in 19 major trials comparing statin therapy with a placebo (or dummy tablet), plus 30,724 participants in four trials that compared more intensive statin therapy with less intensive statin therapy.
Similar Rates of Reported Side Effects
Across nearly all conditions listed in statin package
leaflets as possible side effects, the frequency of reported symptoms was
similar between people taking statins and those taking a placebo. For instance,
each year 0.2% of participants in the statin groups reported cognitive or
memory problems. The same percentage, 0.2%, was reported among those taking a
placebo.
These findings suggest that while some individuals may
experience symptoms during statin treatment, the medication itself is unlikely
to be responsible in most cases.
Key findings:
- The
analysis found no statistically significant increase in risk for almost
all health issues listed in package leaflets as potential side effects of
statins.
- Statin
use was not associated with a meaningful rise in memory loss or dementia,
depression, sleep problems, erectile dysfunction, weight gain, nausea,
fatigue, headaches, or many other commonly reported symptoms.
- Researchers
did identify a small increase in abnormal liver blood test results,
affecting about 0.1% of patients. However, there was no corresponding rise
in serious liver conditions such as hepatitis or liver failure. This
indicates that changes seen in liver blood tests rarely progress to more
serious liver disease.
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.”
Context From Previous Research
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 been shown that statins can cause a small increase in
blood sugar levels, so people already at high risk may develop diabetes sooner.
Professor Bryan Williams, Chief Scientific and Medical
Officer at the British Heart Foundation, said, “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.”
He continues, “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.”
Revising Statin Information
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.
Reference: “Assessment of adverse effects attributed to
statin therapy in product labels: a meta-analysis of double-blind randomised
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Herrington, Adrienne Kirby, Rachel O’Connell, Pierre Amarenco, Hiroyuki Arashi,
Philip Barter, D John Betteridge, Michael Blazing, Gerard J Blauw, Marc Bonaca,
Jackie Bosch, Louise Bowman, Eugene Braunwald, Richard Bulbulia, Robert
Byington, Robert Clarke, Michael Clearfield, Stuart Cobbe, Helen M Colhoun,
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Kjekshus, Michael Koren, John LaRosa, Roberto Latini, Eva Lonn, Donata Lucci,
Jean MacFadyen, Peter Macfarlane, Stephen MacMahon, Aldo Maggioni, Roberto
Marchioli, Ian Marschner, Lemuel Moyé, Heather Murray, Sabina Murphy, Andrew
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Peto, Marc Pfeffer, Neil Poulter, Sara Pressel, Mahboob Rahman, Paul M Ridker,
Michele Robertson, Frank Sacks, Roland Schmieder, Patrick W Serruys, Peter
Sever, John Shaw, James Shepherd, Lara Simpson, Peter Sleight, Liam Smeeth,
Luigi Tavazzi, Jonathan Tobert, Gianni Tognoni, Stella Trompet, John Varigos,
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Lars Wilhelmsen, Stephen Wiviott, Junichi Yamaguchi, Robin Young, Salim Yusuf
and Faiez Zannad, 5 February 2026, The Lancet.
DOI:
10.1016/S0140-6736(25)01578-8
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.