The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug? Systematic review of randomized placebo-controlled trials to aid individual patient choice
Abstract
OBJECTIVE: Discussions about statin efficacy in cardiovascular prevention are always based on data from blinded randomized controlled trials (RCTs) comparing statin to placebo; however, discussion of side effects is not. Clinicians often assume symptoms occurring with statins are caused by statins, encouraging discontinuation. We test this assumption and calculate an evidence-based estimate of the probability of a symptom being genuinely attributable to the statin itself. METHODS: We identified RCTs comparing statin to placebo for cardiovascular prevention that reported side effects separately in the two arms. RESULTS: Among 14 primary prevention trials (46,262 participants), statin therapy increased diabetes by absolute risk of 0.5% (95% CI 0.1-1%, p = 0.012), meanwhile reducing death by a similar extent: -0.5% (-0.9 to -0.2%, p = 0.003). In the 15 secondary prevention RCTs (37,618 participants), statins decreased death by 1.4% (-2.1 to -0.7%, p < 0.001). There were no other statin-attributable symptoms, although asymptomatic liver transaminase elevation was 0.4% more frequent with statins across all trials. Serious adverse events and withdrawals were similar in both arms. CONCLUSIONS: Only a small minority of symptoms reported on statins are genuinely due to the statins: almost all would occur just as frequently on placebo. Only development of new-onset diabetes mellitus was significantly higher on statins than placebo; nevertheless only 1 in 5 of new cases were actually caused by statins. Higher statin doses produce a detectable effect, but even still the proportion attributable to statins is variable: for asymptomatic liver enzyme elevation, the majority are attributable to the higher dose; in contrast for muscle aches, the majority are not.
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“For cancer, a meta-analysis of IPD from randomized trials has shown that statins do not have any significant effect on cancer, at least over a period of ∼5 years [223].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [223]
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“As indicated above, reported rates of muscle symptoms are invariably lower in blinded RCTs when compared with those in registries and observational studies, with myalgia rates similar in subjects on statin or placebo.2–4,20,21”
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Cites
Cholesterol Treatment Trialists' (CTT) Collaboration (2010) · The Lancet · doi:10.1016/s0140-6736(10)61350-5 · Cited by 6,550
Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes
Cannon, C. P., Braunwald, E., McCabe, C. H., Rader, D. J., Rouleau, J. L., Belder, R., Joyal, S. V., Hill, K. A., Pfeffer, M. A., & Skene, A. M. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040583 · Cited by 4,938
Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease
LaRosa, J. C., Grundy, S. M., Waters, D. D., Shear, C., Barter, P., Fruchart, J.-C., Gotto, A. M., Greten, H., Kastelein, J. J. P., Shepherd, J., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050461 · Cited by 3,489
External validity of randomised controlled trials: “To whom do the results of this trial apply?”
Rothwell, P. M. (2005) · The Lancet · doi:10.1016/s0140-6736(04)17670-8 · Cited by 2,544
Statins for the primary prevention of cardiovascular disease
Taylor, F., Huffman, M. D., Macedo, A. F., Moore, T. H., Burke, M., Davey Smith, G., Ward, K., Ebrahim, S., & Gay, H. C. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004816.pub5 · Cited by 1,934
Pedersen, T. R. (2005) · JAMA · doi:10.1001/jama.294.19.2437 · Cited by 1,548
Preiss, D. (2011) · JAMA · doi:10.1001/jama.2011.860 · Cited by 1,390
de Lemos, J. A., Blazing, M. A., Wiviott, S. D., Lewis, E. F., Fox, K. A. A., White, H. D., Rouleau, J.-L., Pedersen, T. R., Gardner, L. H., Mukherjee, R., et al. (2004) · JAMA · doi:10.1001/jama.292.11.1307 · Cited by 1,333
Effect of pravastatin on outcomes after cardiac transplantation
Kobashigawa, J. A., Katznelson, S., Laks, H., Johnson, J. A., Yeatman, L., Wang, X. M., Chia, D., Terasaki, P. I., Sabad, A., Cogert, G. A., et al. (1995) · New England Journal of Medicine · doi:10.1056/nejm199509073331003 · Cited by 1,301
Research works printed but not linked: 2
- Taylor F, 2011, Cochrane Database Syst Rev, 1, CD004816
- Calderon RM, 2010, Lancet, 85, 349
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Kelpsch, D. J., Zhang, L., Thierer, J. H., Cruz, A. G. R., Koren, K., Kumar, U., Lin, Y., Hensley, M. R., Sohn, M., Liu, J. O., et al. (2025) · eLife · doi:10.7554/elife.105314
Kelpsch, D. J., Zhang, L., Thierer, J. H., Cruz, A. G. R., Koren, K., Kumar, U., Lin, Y., Hensley, M. R., Sohn, M., Liu, J. O., et al. (2025) · eLife · doi:10.7554/elife.105314.1.sa0
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Kelpsch, D. J., Zhang, L., Thierer, J. H., Koren, K., Kumar, U., Lin, Y., Hensley, M. R., Sohn, M., Liu, J. O., Lectka, T., et al. (2025) · eLife · doi:10.7554/elife.105314.1
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Effet nocebo et statine – Gestion en pratique des effets secondaires musculaires
Bruckert, É. (2026) · EMC - Endocrinologie - Nutrition · doi:10.1016/s1155-1941(25)49400-1
Does Adding Nocebo Avoidance Strategies Increase the Strength of Nocebo Education?
Spotts, E. K., & Geers, A. L. (2026) · European Journal of Health Psychology · doi:10.1027/2512-8442/a000207
Metadata
- Authors
- Finegold, J. A., Manisty, C. H., Goldacre, B., Barron, A. J., & Francis, D. P.
- Affiliations
- Imperial College London (GB)
- London School of Hygiene & Tropical Medicine (GB)
- National Heart and Lung Institute, Imperial College, London, UK
- Corresponding author
- Finegold, Judith A
- Venue
- European Journal of Preventive Cardiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-03-12
- Volume
- 21
- Issue
- 4
- Pages
- 464-474
- ISSN
- 2047-4873 (ISSN-L)
- 2047-4881
- OpenAlex
- W2105299596
- Cited by
- 214
- References
- 35
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 9 · 2023: 9 · 2022: 16 · 2021: 12 · 2020: 13 · 2019: 17 · 2018: 14 · 2017: 19 · 2016: 30 · 2015: 30 · 2014: 28
- FWCI
- 6.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Preventive Cardiology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- National Institute for Health and Care Research (FS/10/038)
- British Heart Foundation (FS 10/038, PG/11/36/2883, FS/10/38/28268)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Keywords
- statins, adverse drug reactions, new-onset diabetes, liver transaminase elevation, muscle aches, cardiovascular disease prevention, primary prevention, secondary prevention, statin dose
- MeSH terms
- Diabetes Mellitus, Dose-Response Relationship, Drug, Humans, Liver, Muscular Diseases, Risk Factors, Biomarkers, Placebo Effect, Randomized Controlled Trials as Topic, Treatment Outcome, Risk Assessment, Hydroxymethylglutaryl-CoA Reductase Inhibitors
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