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Assessment and management of statin-associated muscle symptoms (SAMS): A clinical perspective from the National Lipid Association
Open accessAbstract
Statin-associated muscle symptoms (SAMS) are the most common form of statin intolerance and are associated with increased risk of cardiovascular events that manifest from statin underutilization and discontinuation. The reported frequencies of SAMS are divergent in the literature. The writing group estimates the prevalence of SAMS, namely all muscle symptoms temporally related to statin use but without regard to causality, to be about 10% (range 5% to 25%), and the prevalence of pharmacological SAMS, specifically muscle symptoms resulting from pharmacological properties of the statin, to be about 1-2% (range 0.5% to 4%). In clinical practice, SAMS are likely to result from a combination of pharmacological and nonpharmacological effects, however this does not make the symptoms any less clinically relevant. Regardless of the etiology, SAMS need to be addressed in accordance with patients' preferences and experiences. This clinical perspective reviews the epidemiology and underlying pathophysiology of SAMS, and the cardiovascular consequences resulting from statin discontinuation. We present patient-centered clinical and communication strategies to mitigate SAMS and improve medication adherence and outcomes among statin users. Treatment strategies include 1) optimizing lifestyle interventions, 2) modulating risk factors that may contribute to muscle symptoms, 3) optimizing statin tolerability by dose reduction, decreased dosing frequency, or use of an alternate statin with more favorable pharmacokinetic properties, and 4) use of non-statins, emphasizing those with evidence for atherosclerotic risk reduction, either in combination with or in place of statin therapy depending on the patient's circumstances. The focus of this clinical perspective is sustainable lipoprotein goal achievement, which is important for cardiovascular risk reduction.
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“Recent narrative reviews on the management of SAMS found that further research is needed to close the knowledge gap [19].”
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Cites
Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease
Sabatine, M. S., Giugliano, R. P., Keech, A. C., Honarpour, N., Wiviott, S. D., Murphy, S. A., Kuder, J. F., Wang, H., Liu, T., Wasserman, S. M., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1615664 · Cited by 6,138
Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes
Cannon, C. P., Blazing, M. A., Giugliano, R. P., McCagg, A., White, J. A., Theroux, P., Darius, H., Lewis, B. S., Ophuis, T. O., Jukema, J. W., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1410489 · Cited by 4,487
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Helsinki Heart Study: Primary-Prevention Trial with Gemfibrozil in Middle-Aged Men with Dyslipidemia
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- Lloyd-Jones, 2022, J. Am. Coll. Cardiol
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Items 101–111 of 111
Huynh, T., Nguyen, H., & Nguyen, M. (2026) · Journal of Lipid and Atherosclerosis · doi:10.12997/jla.2026.15.1.183
Kang, W., Costa, A., Medeiros, J. I. M., Cicali, B., Salgado, W., Schmidt, S., & de Moraes, N. V. (2026) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.70163
“10 41 When experiencing muscle symptoms, elevation in creatine kinase (CK) levels should be monitored.”
Predictors of statin intolerance among statin users in primary care using real-world dataPreprint
Rakhshanda, S., Liaw, S., Rhee, J., Rye, K., & Jonnagaddala, J. (2026) · medRxiv · doi:10.64898/2026.02.23.26346866
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Statin-Related Myotoxicity: A Narrative Review and Practical Approach for General Internists
Ng, I. K. S., Teo, K. S., Yang, H., Goh, W. G. W., Thong, C. Z. Y., Tan, L. F., Teo, D. B. S., & Mak, A. (2026) · Journal of General Internal Medicine · doi:10.1007/s11606-026-10563-8
“34 If their symptoms and/or CK levels resolve with statin discontinuation, they could either be re-challenged on a lower dose, trialed on an alternative statin (such as switching from lipophilic statin to hydrophilic statin, or to a statin that has a different metabolism profile less susceptible to…”
A severe and fatal course of statin-induced necrotizing autoimmune myopathy: a case report
Saleh, A., Sighaka, D. S., Panyala, N., Abid, H., Batarseh, M., & Yuhico, R. J. O. (2026) · Journal of Medical Case Reports · doi:10.1186/s13256-026-06310-6
“However, no clear link between these properties and statin-induced necrotizing myopathy was established [4, 5].”
Al-Qurain, A. A., Alsultan, A. K., Alamoudi, M. K., Almohaywi, M., Shakoori, A., Gharash, H. A., Alsaffar, N., & Alrossies, A. S. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2026.1903467
“Although statins are generally well tolerated, concerns regarding statin-associated muscle symptoms (SAMS) remain one of the most common reasons for treatment discontinuation or reduced adherence (4 – 6).”
InfluentialMiyamoto, M. I., Ko, C., Chiu, S., Miyamoto, G., Coy, C., Mumtaz, S., Loussararian, A. H., El-Haj-Ibrahim, F., & Brown, S. M. (2026) · Journal of clinical lipidology · doi:10.1016/j.jacl.2026.08.022
Zhang, Y., Su, J., Zhong, L., Shang, L., & Wan, H. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1942019
“Typical SAMS usually develop within 4 – 8 weeks of treatment, present as bilateral symmetrical myalgia, improve after withdrawal, and rarely cause marked enzyme elevation (23).”
Huang, J., Fan, Z., & Ding, Y. (2026) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1155/jcpt/3306258
Killion, M. R., Yao, J., Newman, R., Gutta, A. A., & Tou, J. C. L. (2026) · Dietetics · doi:10.3390/dietetics5040062
Metadata
- Authors
- Warden, B. A., Guyton, J. R., Kovacs, A. C., Durham, J. A., Jones, L. K., Dixon, D. L., Jacobson, T. A., & Duell, P. B.
- Affiliations
- Oregon Health & Science University (US)
- Duke Medical Center (US)
- Virginia Commonwealth University (US)
- Emory University (US)
- Corresponding author
- Warden, Bruce A.
- Guyton, John R.
- Kovacs, Adrienne C.
- Durham, Jessica A.
- Jones, Laney K.
- Dixon, Dave L.
- Jacobson, Terry A.
- Duell, P. Barton
- Venue
- Journal of Clinical Lipidology
- Publisher
- Elsevier BV
- Published
- 2023-01
- Volume
- 17
- Issue
- 1
- Pages
- 19-39
- ISSN
- 1876-4789 (ISSN-L)
- 1933-2874
- OpenAlex
- W4295221059
- Cited by
- 111
- References
- 82
- Citations by year
- 2026: 24 · 2025: 40 · 2024: 24 · 2023: 21
- FWCI
- 20.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of clinical lipidology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Family Practice › Medication Adherence and Compliance
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- statin-associated muscle symptoms, statin intolerance, statin discontinuation, cardiovascular risk, medication adherence, lifestyle intervention, statin dose reduction, non-statin therapy, cardiovascular risk reduction
- MeSH terms
- Humans, Lipids, Muscles, Muscular Diseases, Risk Factors, Hydroxymethylglutaryl-CoA Reductase Inhibitors
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